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Study Design: Retrospective cohort study.Purpose: To evaluate the efficacy of our current prophylactic strategy by investigating the incidence of subsequent vertebral body fractures (SVBFs) following balloon kyphoplasty (BKP).Overview of Literature: Although extensive studies have investigated the risk factors for SVBFs after BKP, few have reported on postoperative therapies to prevent SVBFs and have evaluated their effectiveness.Methods: This study enrolled 273 patients who underwent an initial BKP. To treat osteoporosis, parathyroid hormone (PTH) administration was started 1–2 weeks before BKP and continued for at least 6 months postoperatively. Corsets were applied for 3 months after the procedure. Rehabilitative interventions, including hip range-of-motion training, muscle strengthening exercises, and motion/posture instruction, were started from the preoperative assessment time point and resumed 3 hours postoperatively. Corsets were used in all patients. Therefore, no grouping based on corset use was performed. PTH was used in 180 patients, and they were divided into the following two groups: PTH user group and PTH nonuser group. Rehabilitative interventions were provided to all patients for a median duration of 17 days. Patients who underwent rehabilitative intervention for

Background Medication-related osteonecrosis of the jaw (MRONJ) is a potentially severe adverse side effect of antiresorptive agents. However, withdrawal of antiresorptive agents in patients with osteoporosis may increase the risk of fractures. The treatment of MRONJ is challenging and standard treatment guidelines have yet to be established. In this study, the aim was to examined whether adjunct daily or weekly teriparatide (TPTD) injections are beneficial for the bone exposure of MRONJ lesions compared to standard conservative management. We also studied the complications and patients’ responses to TPTD therapy. Methods We enrolled 27 patients, from January 2012 until December 2016, with chronic and refractory MRONJ. There were 4 men and 23 women, with 85% of the total number being females. Nine patients who did not select TPTD therapy for several reasons formed the non-TPTD group and the remaining 18 patients were randomly assigned to the daily (n=9) or weekly (n=9) groups. All subjects in both TPTD groups continued standard conservative therapy in addition to their daily or weekly subcutaneous injection of TPTD. The daily group received a daily injection of TPTD (20 μg) and the weekly group received a weekly injection of TPTD (56.5 μg). We evaluated the complications and benefits of TPTD therapy of MRONJ. Results Three patients in the daily group did not complete the study, resulting in six patients in the daily group, nine patients in the weekly group, and nine patients in the non-TPTD group for the final analysis. Each patient in TPTD group demonstrated complete coverage of the exposed bone with normal mucosa. The TPTD group showed a shorter healing period compared to the non-TPTD group. There were no complications of atypical fractures of the femoral head in any patient. Conclusions Daily and weekly TPTD treatment resulted in a shortened treatment period compared with standard conservative therapy with no increase in the rate of complications or worsening of osteoporosis.

OBJECTIVE Teriparatide (TPTD) is a potent promoter of early-stage osteogenesis and may be a useful adjuvant therapy to reduce complications related to bone fragility in spinal surgery patients with osteoporosis. However, effective neoadjuvant TPTD therapy regimens remain poorly understood. This study aimed to examine the effect of preoperative TPTD administration on cancellous bone with bone histomorphometry and to clarify the timing of preoperative TPTD administration for patients with spinal fusion and osteoporosis. METHODS In this longitudinal multicenter study, 57 patients with spinal fusion and osteoporosis, who consented to undergo iliac biopsy, were allocated to the following treatment groups: neoadjuvant TPTD therapy group (n = 42) and no neoadjuvant therapy (NTC) group (n = 15). Patients in the TPTD group were categorized into subgroups on the basis of duration of preoperative TPTD administration, as follows: 1 month (n = 9), 2 months (n = 8), 3 months (n = 9), 4 months (n = 7), and 6 months (n = 9). All patient samples were preoperatively double labeled with tetracycline, and iliac biopsies were performed during spinal fusion surgery. Histomorphometric analyses were performed on nondecalcified, thin-sliced specimens. Specimens were classified on the basis of TPTD administration duration and subsequently compared with those of the NTC group. Postoperative complications and Oswestry Disability Index scores were evaluated at 1 and 2 years after surgery. RESULTS There were no demographic differences between groups. Mineralizing surface/bone surface, a key parameter of dynamic bone formation, started to increase after 1 month of TPTD administration; this increase became significant after 3 months of administration and peaked at 4 months, with a 6-fold increase relative to that of the NTC group. The patients who received preoperative TPTD for 3 months or more had superior clinical results in terms of the osteoporotic complication rate and Oswestry Disability Index scores, except for bisphosphonate-pretreated patients. CONCLUSIONS When considering neoadjuvant TPTD therapy, the authors recommend at least 3 months of preoperative administration to provide a more substantial anabolic effect from the early postoperative stage.

Abstract:: As a common systemically muscular-skeleton disorder of aging, osteoporosisis is characterized by the uninterrupted deconstruction in osseous microarchitecture. Osteoporosis can consequently lead to a significantly high risk of osteoporotic fractures, such as osteoporotic vertebral compressive fractures [OVCF] in the spine and osteoporotic femoral neck fractures in the hip joint, which can significantly increase the numbers of mortality and morbidity in elderly people, especially in postmenopausal women. In addition, vitamin K has been demonstrated to play a key role in inhibiting osteoporotic fractures among postmenopausal women, but its long-term benefits, potential harms, and side effects of the combination between vitamin K and other anti-osteoporosis medicines, such as bisphosphonates or teriparatide still remain to be extensively studied.Therefore, the present study aimed to systematically reviewed previously published literature on the role of vitamin K in the treatment of osteoporosis.We currently, via multiple query strategies, searched the relevant literature in Cochrane and PubMed from January 2010 to December 2019. Subsequently, we conducted the systematic review according to the standard guideline of Preferred Reporting Item for Systematic Reviews and Meta-Analyses [PRISMA]. Finally, ten relevant studies met our current criteria for inclusion; subsequently, we followed the PRISMA guideline, then systematically reviewed each study by categorizing the data sources and analytical approaches in each study, while setting up variables and defining each study's outcomes.

Distraction osteogenesis has been used for post-traumatic segmental bone defects. Absent or delayed callus formation in the distraction gap can lead to significant morbidity and affect the clinical outcome. Experimental evidence in animal models has demonstrated that teriparatide enhances the consolidation of regenerate and also strengthens it. This study aimed to report our experience with recombinant teriparatide therapy for patients with regenerate insufficiency.Nine out of 43 patients undergoing limb lengthening using the limb reconstruction system (LRS) fixator were diagnosed with regenerate insufficiency. With informed consent, these patients received a therapeutic regime of 20 μg of teriparatide administered subcutaneously once daily for a period of 3 months.The mean age in the sample was 40.22 years (SD 17.87). Regenerate insufficiency was diagnosed at a mean of 4.94 months (range 2.5-9 months) from surgery. Teriparatide injections were started at a mean of 6.94 months (range 4.5-11 months) from surgery. The sites of regenerate insufficiency were tibia (The initiation of teriparatide treatment as described in this study may be successful in triggering the osteogenic potential within poor regenerate and help in consolidation and avoid more invasive surgical procedures.Patil B, Kansay R, Gupta S

Context We have previously reported that teriparatide is associated with substantial increases in bone mineral density (BMD) at the lumbar spine (LS), total hip (TH), and femoral neck (FN) and small declines at the distal radius in 41 premenopausal women with idiopathic osteoporosis (IOP), all severely affected with low trauma fractures and/or very low BMD. Effects of teriparatide dissipate if not followed by antiresorptives. Objective To assess the effects of 12 and 24 months of denosumab in premenopausal women with IOP completing 24 months of teriparatide. Methods This was a preplanned phase 2B extension study. Premenopausal women with IOP who had completed a course of teriparatide received denosumab 60 mg every 6 months over 24 months. The main outcome measure was within-group change in BMD at the LS at 12 months. Secondary outcomes include change in 12-month BMD at other sites, 24-month BMD at all sites, trabecular bone score (TBS), and bone turnover markers (BTMs). Results After completing teriparatide, 32 participants took denosumab for 12 months and 29 for 24 months, with statistically significant increases in BMD at the LS (5.2 ± 2.6% and 6.9 ± 2.6%), TH (2.9 ± 2.4% and 4.6 ± 2.8%), and FN (3.0 ± 3.8% and 4.7 ± 4.9%). Over the entire 24-month teriparatide and 24-month denosumab treatment period, BMD increased by 21.9 ± 7.8% at the LS, 9.8 ± 4.6% at the TH, and 9.5 ± 4.7% at the FN (all P < .0001). TBS increased by 5.8 ± 5.6% (P < .001). Serum BTM decreased by 75% to 85% by 3 months and remained suppressed through 12 months of denosumab. Denosumab was generally well tolerated. Conclusion These data support the use of sequential teriparatide and denosumab to increase BMD in premenopausal women with severe osteoporosis.

Snyder-Robinson syndrome is an extremely rare genetic disorder, caused by mutations of the spermine synthase gene. We report a novel case of Snyder-Robinson syndrome, caused by a de novo mutation and first misdiagnosed with osteogenesis imperfecta. Clinical features, course, and genetic analysis are presented. The patient was treated with bisphosphonates for a decade, until developing an atypical femoral fracture. Teriparatide was then administered for 2 years and then changed to denosumab every 6 months, improving his bone density mass and preventing further fractures.

Osteoporosis (OP) in men is a heterogeneous disease that has received little attention. Traditionally, OP was considered a di­sease affecting only women. The developed attitude towards male OP as a rare pathology and the lack of alertness lead to the fact that many patients remain untreated. However, one third of the worldwide hip fractures occur in the male population, which results in a high level of disability and premature mortality. The problem of diagnosis and treatment of OP in recent years is becoming increasingly relevant in connection with the population ageing and those complications that are typical for this disease. The frequency of OP-associated fractures in men is similar to the frequency of myocardial infarction and is superior to the incidence of lung carcinoma and prostate cancer. Outcome for male patients after a hip fracture looks frustrating: one third (32 %) dies during the first year after the hip fracture, and only 21 % are able to live independently in society for one year after the fracture. This problem is most common in people over 70 years old. The etiology of male OP can be idiopathic or secondary due to hypogonadism, vitamin D deficiency and inadequate calcium intake, hormonal treatment of prostate cancer, concomitant pathologies, the use of drugs that affect the bone metabolism. In the present review, based on the European and American current guidelines, the issues of male OP epidemiology, the main principles of the disease diagnosis are reviewed, based on the evaluation data of clinical mani-festations, anamnesis information, including targeted screening. The algorithm FRAX application allows patients to start treatment at a stage when bone mineral density is within the range of osteopenic values and there are additional risk factors. Methods of instrumental and laboratory examination of patients are described in detail. The main methods of treatment are highlighted, first-line drug for the treatment of males are bisphosphonates (alendronate, risedronate, zoledronic acid) and teriparatide, the second line is denosumab. Despite the fact that the evidence base for these drugs is precisely small in men, modern data do not suggest gender differences in treatment outcome with similar values of bone mineral density. All these agents inhibit bone resorption, with the exception of teriparatide, which promotes a new bone growth. Timely diagnosis and prophylaxis of OP in men may contribute to early detection, will allow the initiation of the adequate therapy and reduce the number of fractures in such patients.

Glucocorticoids are of substantial therapeutic importance in the treatment of inflammatory diseases, but are also associated with bone mineral density loss, osteoporosis, and fractures, especially with long-term use.To develop recommendations for the management of glucocorticoid-induced osteoporosis (GIOP) in adult patients on long-term glucocorticoid (GC) treatment.A systematic literature search (SLR) was conducted to synthesize the evidence for GIOP prevention and treatment options. Recommendations were developed based on SLR/level of evidence and by previously defined questions and in a structured group consensus process.Recommendations include supplementation with calcium and vitamin D under long-term GC therapy in adults. If specific osteologic treatment is indicated, we recommend bisphosphonates or denosumab as first-line treatment. If fracture risk is high, we recommend teriparatide as primary specific osteologic treatment. Denosumab should be used in cases of severe renal insufficiency, and specific osteologic treatment should not be given in pregnancy. For patients who have not reached the treatment goal, a switch to another class of specific osteologic drugs should be performed. We recommend re-evaluation after a treatment duration of 3-5 years or after termination of long-term GC treatment.This work aims to provide evidence-based and consensus-based recommendations for the best possible management of GIOP in Germany and to support treatment decisions.HINTERGRUND: Glukokortikoide sind von erheblicher therapeutischer Bedeutung bei der Behandlung entzündlicher Erkrankungen, jedoch insbesondere bei langfristiger Anwendung mit Knochenmineraldichteverlust, Osteoporose und Frakturen assoziiert.Es sollten Empfehlungen zum Management der Glukokortikoid-induzierten Osteoporose (GIOP) bei erwachsenen Patienten unter Langzeit-Glukokortikoid(GC)-Therapie entwickelt werden.Es wurde eine systematische Literatursuche (SLR) durchgeführt, um die Evidenz für Präventions- und Behandlungsoptionen der GIOP zusammenzufassen. Mithilfe zuvor definierter Fragestellungen wurden, basierend auf SLR und dem Evidenzgrad, Empfehlungen in einem strukturierten Gruppenkonsensprozess erarbeitet.Die Empfehlungen umfassen zunächst die Supplementation mit Kalzium und Vitamin D bei Erwachsenen unter Langzeit-GC-Therapie. Wenn eine spezifische osteologische Therapie angezeigt ist, empfehlen wir als Erstlinientherapie Bisphosphonate oder Denosumab. Bei hohem Frakturrisiko empfehlen wir Teriparatid als primäre spezifische osteologische Therapie. Bei hochgradiger Niereninsuffizienz soll Denosumab (nach Ausschluss renaler Osteopathie) eingesetzt werden und bei Schwangerschaft keine spezifische osteologische Therapie erfolgen. Für Patienten, die das Therapieziel nicht erreicht haben, sollte die Umstellung auf eine andere Klasse spezifischer osteologischer Medikamente erfolgen. Wir empfehlen eine Reevaluation nach einer Therapiedauer von 3 bis 5 Jahren oder nach Beendigung der Langzeit-GC-Therapie.Diese Arbeit soll evidenz- und konsensbasierte Empfehlungen für ein bestmögliches Management der GIOP in Deutschland geben und bei Behandlungsentscheidungen unterstützen.

The aim of this study was to investigate the characteristics of postmenopausal women prescribed with teriparatide in Slovenia, during the first decade after its approval, and the predictors of bone mineral density (BMD) improvement with treatment. We retrospectively studied postmenopausal osteoporotic patients prescribed with teriparatide at tertiary center from 2006 to 2015. BMD was measured at standard sites by DXA at baseline, after 12 and 24 months. 25-hydroxyvitamin D and procollagen type I N-terminal propeptide (PINP) were measured at the same time-points. The inclusion criteria were met by 188 women (aged 71 years on average), 151 (80.3%) with postmenopausal and 37 (19.7%) with glucocorticoid-induced osteoporosis. Everyone had at least one fracture, 159 (84.6%) had ≥2 fractures, with vertebral fractures in 172 patients (91.5%). All patients had been previously on antiresorptives for 8.6 years on average. The average BMD change at lumbar spine, total hip, and femoral neck was +5.0%, −1.1%, and +0.3% after 24 months of treatment, respectively. Higher baseline PINP was associated with higher BMD increase at all sites after the first 12 months. Teriparatide was prescribed mostly to elderly women with severe osteoporosis who had sustained two or more fractures despite long-term antiresorptive therapy. Baseline PINP might predict initial BMD increase with teriparatide.

Objective To provide a systematic review about the efficacy and safety of romosozumab and teriparatide for the treatment of postmenopausal osteoporosis. Method Randomized controlled trials (RCTs) were searched from electronic databases, including PubMed (1996 to June 2019), Embase (1980 to June 2019), Cochrane Library (CENTRAL, June 2019), Web of Science (1998 to June 2019), and others. The primary outcomes included the following: the percentage change in bone mineral density of lumbar spine and total hip from baseline at month 6 and month 12 in each group. The secondary outcomes included the following: the percentage change in bone mineral density of femoral neck from baseline at month 6 and month 12 in each group and the incidence of adverse events at month 12 in each group. Results Four studies containing 1304 patients met our selection criteria. The result of our analysis indicated that romosozumab showed better effects in improving BMD of lumbar spine (month 6: MD = 3.54, 95% CI [3.13, 3.94], P, To provide a systematic review about the efficacy and safety of romosozumab and teriparatide for the treatment of postmenopausal osteoporosis, Randomized controlled trials were searched from electronic database and then articles were screened according to inclusion and exclusion criteria. Risk of bias were assessmented, and statistical analysis and data synthesis were conducted with GRADE system to evaluate the level of the evidence. Our results demonstrate that romosozumab was better than teriparatide both in terms of efficacy and side effects.

Denosumab discontinuation results in rapid bone loss and increased risk of multiple rebound-associated vertebral fractures (RAVFs). The optimal treatment for patients who have sustained such fractures is currently unknown. We aimed to investigate the bone mineral density (BMD) changes achieved with various regimens in postmenopausal women who had sustained RAVFs after denosumab discontinuation in everyday clinical practice. In this multicenter, retrospective observational study, 39 Greek postmenopausal women from six regional bone centers throughout Greece with RAVFs after denosumab discontinuation were included. We collected BMD and fracture data before and 1 year after treatment with denosumab (n = 20), teriparatide (n = 8), zoledronate (n = 8) or teriparatide/denosumab combination (n = 3). Both lumbar spine (LS)-- and femoral neck (FN)-BMD were preserved with all regimens used. With the exception of zoledronate, a trend towards increase was observed with all regimens in LS-BMD. Three patients sustained additional fractures despite treatment reinstitution (2 with zoledronate and 1 with teriparatide). Among patients with RAVFs following denosumab discontinuation both antiresorptive (zoledronate and denosumab) and anabolic (teriparatide) treatment as well as the combination of denosumab with teriparatide seem to be effective in terms of BMD response.

The 2020 American Association of Clinical Endocrinologists guidelines for assessing osteoporosis among postmenopausal women stratified postmenopausal women with osteoporosis to "high" and "very-high" fracture risk categories and recommended anabolic agents as initial therapy followed by an antiresorptive agent. Switching the order can blunt the effect of anabolic agents, and failing to follow with an antiresorptive can lead to loss of bone generated by the anabolic agent. It would be helpful to understand the real-world prescribing patterns of anabolic agents. Using the 2010-2015 Medicare 100% osteoporosis database, we assessed patient profiles, teriparatide prescribers, persistence of teriparatide therapy, and antiresorptive agent use after teriparatide discontinuation among elderly women who initiated teriparatide from 2011 to 2013. This study included 14,786 patients. In the year before teriparatide initiation, 30.0% of them had a fracture, 67.6% had a dual energy x-ray absorptiometry scan, 74.4% had a diagnosis of osteoporosis, and 47.9% used antiresorptive agents (non-naïve teriparatide users). Among those who had fractures, 49.4% initiated teriparatide within 3 months postfracture. Teriparatide was prescribed for 37% of users by primary care doctors, 19% by rheumatologists, 13% by endocrinologists, and 7.0% by orthopedists. Median time of teriparatide use was 7.2 months. After teriparatide discontinuation, 40.8% switched to antiresorptive agents (31.9% among naïve teriparatide users, 50.5% among non-naïve users). Among switchers, 42.5% switched within 60 days, 50.5% switched to denosumab, and 31.6% switched to oral bisphosphonates. This study of real-world prescribing data found that about half of teriparatide users switched from an antiresorptive agent, and less than half switched to antiresorptive agents after teriparatide discontinuation. Persistence of teriparatide use was suboptimal. In the management of postmenopausal osteoporosis, increasing the persistence of teriparatide use and improving the appropriate treatment sequence of anabolic and antiresorptive drugs are critical to maximizing gains in bone mass, providing the greatest protection against fractures. © 2021 American Society for Bone and Mineral Research (ASBMR).

Over the past few decades, the number of endoprosthetic joint replacements has steadily increased. Most of these patients are of higher age and due to osteoporosis may have a reduced bone quality. In te case of patients with joint replacements and osteoporosis the following complications are often seen: intraoperative periprosthetic fractures, periprosthetic osteolysis, increased implant migration or postoperative periprosthetic fractures. We present a literature review on issues of osteoporosis in patients with endoprosthetic joint replacements. Evaluation of bone quality seems a essential point in patient management to provide the best possible care and to optimize long term surgical outcomes. If necessary, patients should be educated about a possible calcium and vitamin D supplementation. In addition, it seems reasonable to aim for physiological vitamin D levels perioperatively. In postmenopausal women, men over 70 years and both women and men with an increased risk of osteoporosis within two years of implantation of a total joint replacement a bone mineral density measurement should be performed. In patients with reduced bone quality, treatment with bisphosphonates, denosumab or teriparatide should be considered as to improve the osseous integration of cementless implants, and increase the lifespan of implants as well as to reduce periprosthetic fractures and fractures in general. In individual cases of patients with osteoporosis cementation of prosthetic components (especially in total hip replacements) may be required., За последние несколько десятилетий количество эндопротезирований суставов неуклонно возрастает. Большинство таких пациентов — старшего возраста, и из-за остеопороза качество костной ткани у них снижается. У пациентов с остеопорозом, перенесших замену сустава, часто наблюдаются следующие осложнения: интраоперационные перипротезные переломы, перипротезный остеолиз, увеличение миграции имплантатов или послеоперационные перипротезные переломы. Мы представляем обзор литературы по проблемам остеопороза у пациентов, перенесших эндопротезирование сустава. Оценка качества костной ткани является важным моментом при лечении пациентов в плане обеспечения наилучшего ухода и оптимизирования долгосрочных хирургических результатов. При необходимости больных следует проинформировать о возможности нутритивной поддержки препаратами кальция и витамина D. Кроме того, в периоперационном периоде целесообразно достижение физиологических уровней витамина D. У женщин в постменопаузальном периоде, мужчин старше 70 лет, женщин и мужчин с повышенным риском развития остеопороза в течение двух лет после полной замены сустава следует выполнять оценку минеральной плотности кости. У пациентов с пониженным качеством костной ткани следует рассмотреть возможность лечения бисфосфонатами, деносумабом или терипаратидом для улучшения остеоинтеграции бесцементных имплантатов, увеличения срока службы имплантатов, а также для сокращения перипротезных переломов и переломов в целом. В отдельных случаях пациентам с остеопорозом может потребоваться использование цементных протезных компонентов (особенно при тотальном эндопротезировании тазобедренного сустава)., За останні кілька десятиліть кількість ендопротезувань суглобів неухильно зростає. Більшість таких пацієнтів — старшого віку, і через остеопороз якість кісткової тканини у них знижується. У пацієнтів з остеопорозом, які перенесли заміну суглоба, часто спостерігаються такі ускладнення: інтраопераційні перипротезні переломи, перипротезний остеоліз, збільшення міграції імплантатів або післяопераційні перипротезні переломи. Ми надаємо огляд літератури з проблем остеопорозу в пацієнтів, які перенесли ендопротезування суглоба. Оцінка якості кісткової тканини є важливим моментом при лікуванні пацієнтів щодо забезпечення найкращого догляду та оптимізування довгострокових хірургічних результатів. При необхідності хворих слід поінформувати про можливість нутритивної підтримки препаратами кальцію і вітаміну D. Крім того, в періопераційному періоді доцільно досягнення фізіологічних рівнів вітаміну D. У жінок у постменопаузальному періоді, чоловіків віком понад 70 років, жінок і чоловіків з підвищеним ризиком розвитку остеопорозу протягом двох років після повної заміни суглоба слід виконувати оцінку мінеральної щільності кістки. У пацієнтів зі зниженою якістю кісткової тканини слід розглянути можливість лікування бісфосфонатами, деносумабом або терипаратидом для поліпшення остеоінтеграції безцементних імплантатів, збільшення терміну служби імплантатів, а також для скорочення перипротезних переломів і переломів взагалі. В окремих випадках пацієнтам з остеопорозом може знадобитися використання цементних протезних компонентів (особливо при тотальному ендопротезуванні кульшового суглоба).

BACKGROUND Osteoporosis is a metabolic bone disease that commonly affects the elderly. Degenerative spinal disease that may require surgical intervention is also prevalent in this susceptible population. If undiagnosed or untreated before spine surgery, osteoporosis may result in an increased risk of postoperative adverse events. Nontreatment of osteoporosis preoperatively may be related to a poor understanding of bone physiology, a lack of standardized treatment algorithms, limited cost-effective interventions, and reluctance by spine surgeons to be the primary provider of osteoporosis management. OBJECTIVE The objective of this evidence-based review is to develop guidelines for the preoperative assessment and treatment of osteoporosis in patients undergoing spine surgery. METHODS A systematic review of the literature was performed using the National Library of Medicine/PubMed database and Embase for studies relevant to preoperative diagnostic studies that predict increased risk of osteoporosis-related postoperative adverse events and whether the preoperative treatment of low bone mineral density (BMD) in patients with osteoporosis improves outcome. RESULTS Out of 281 studies, 17 met the inclusion criteria and were included for systematic review. The task force affirmed a Grade B recommendation that preoperative osteoporosis testing with a dual-energy X-ray absorptiometry scan (T-score < -2.5), a computed tomography scan (Hounsfield units

The number of patients on long-term anti-osteoporotic drug therapy is rising. Unfortunately, there are few data to guide decisions about duration of pharmacologic therapy for osteoporosis. Many practitioners discontinue therapy after a period of 5 years because of the risk of rare but severe side effects that may occur in long-term users. The objective of this narrative review was to describe the effects of discontinuation of anti-osteoporotic drugs and to investigate what is not yet known on this topic. For each anti-osteoporotic agent, PubMed was searched for evidence from randomized clinical trials in patients with osteoporosis on osteoporotic drugs lasting ≥ 3 years, followed by ≥ 1 year of follow-up after discontinuation of therapy and reported at least one item of the following: changes in bone mineral density, bone turnover markers and/or the risk of vertebral and/or nonvertebral fractures after discontinuation of therapy. The% change in bone mineral density (BMD) after 1 year of discontinuation of therapy is − 0.4% or less at the hip and femoral neck in both alendronate- and zoledronic acid-treated patients. In the other reported agents (risedronate, ibandronate, raloxifene, teriparatide, denosumab and romosozumab) this percentage of bone loss at the femoral neck and total hip was at least 1%, with the largest decrease in BMD after discontinuation of denosumab and romosozumab. In all studies reporting bone turnover markers, a substantial rapid rise in these markers was observed after discontinuation of therapy, with a large rebound increase to far above baseline levels in the denosumab-treated patients. There were few data on fracture risk after discontinuation of therapy; data showed that discontinuing alendronate, zoledronic acid and especially denosumab significantly increases the risk of vertebral fractures. In conclusion, osteoporosis should be considered more as a chronic condition. Therefore, in modern fracture risk management, continuous monitoring and treatment is required, as is the case with other chronic diseases, to sustain the benefits of therapy, especially in denosumab- and romosozumab-treated patients. The exception is alendronate and zoledronic acid, in these patients a discontinuation of drug therapy of 1 year or more might be acceptable.

The Asian and Latin America Fracture Observational Study (ALAFOS) is a prospective, observational, single-arm study conducted in 20 countries across Asia, Latin America and the Middle East. ALAFOS evaluated new clinical vertebral and non-vertebral fragility fractures in relation to time on teriparatide, in postmenopausal women with osteoporosis in real-life clinical practice. Clinical fragility fractures, back pain, and health-related quality of life (HRQoL) were recorded in 6-month intervals for ≤ 24 months during teriparatide treatment and up to 12-months post-treatment. Data were analysed with piecewise exponential regression with inverse probability weighting for time to event outcomes and mixed-model repeated measures for back pain and HRQoL. 3054 postmenopausal women started teriparatide and attended ≥ one follow-up visit (mean [SD] age 72.5 [10.4] years). The median (95% CI) time to treatment discontinuation was 22.0 months (21.2, 22.8). During the treatment period, 111 patients (3.6%) sustained 126 clinical fractures (2.98 fractures/100 patient-years). Rates of new clinical fragility fractures were significantly decreased during the > 6–12, > 12–18, and > 18–24-month periods, as compared with the first 6 months of treatment (hazard ratio [HR] 0.57; 95% CI 0.37, 0.88; p = 0.012; HR 0.35; 95% CI 0.19, 0.62; p p = 0.011; respectively). Patients also reported an improvement in back pain and HRQoL (p

Aim: The aim of the study is to assess the Pharmacological management of osteoporosis in postmenopausal women. Objective: The purpose of this study is to evaluate the treatment of osteoporosis in postmenopausal women. Methodology: This is an observational prospective study, carried out in a tertiary care hospital. Results: A total of 300 postmenopausal women were enrolled in the study. The mean ± standard deviation, of the age of postmenopausal women included in this study was 55.5 ± 5.0 years. 68.1% were prescribed with the combinational therapy of Teriparatide+Bisphosphonates. 39.2% of subjects were using acetaminophen for pain. Conclusion: Antiresorptive drugs (hormonal therapy, bisphosphonates, and denosumab) and, the anabolic agents (teriparatide) are commonly prescribed, in this study it is obvious that Sequential Therapy is highly prevailing in the clinical practice, with 68.1%.

Pelvic fracture patients were randomized to blinded daily subcutaneous teriparatide (TPTD) or placebo to assess healing and functional outcomes over 3 months. With TPTD, there was no evidence of improved healing by CT or pain reduction; however, physical performance improved with TPTD but not placebo (group difference p0.03).To determine if teriparatide (20 μg/day; TPTD) results in improved radiologic healing, reduced pain, and improved functional outcome vs placebo over 3 months in pelvic fracture patients.This randomized, placebo-controlled study enrolled 35 patients (women and men50 years old) within 4 weeks of pelvic fracture and evaluated the effect of blinded TPTD vs placebo over 3 months on fracture healing. Fracture healing from CT images at 0 and 3 months was assessed as cortical bridging using a 5-point scale. The numeric rating scale (NRS) for pain was administered monthly. Physical performance was assessed monthly by Continuous Summary Physical Performance Score (based on 4 m walk speed, timed repeated chair stands, and balance) and the Timed Up and Go (TUG) test.The mean age was 82, and80% were female. The intention to treat analysis showed no group difference in cortical bridging score, and 50% of fractures in TPTD-treated and 53% of fractures in placebo-treated patients were healed at 3 months, unchanged after adjustment for age, sacral fracture, and fracture displacement. Median pain score dropped significantly in both groups with no group differences. Both CSPPS and TUG improved in the teriparatide group, whereas there was no improvement in the placebo group (group difference p0.03 for CSPPS at 2 and 3 months).In this small randomized, blinded study, there was no improvement in radiographic healing (CT at 3 months) or pain with TPTD vs placebo; however, there was improved physical performance in TPTD-treated subjects that was not evident in the placebo group.

Osteoporosis is a common chronic condition that markedly increases the risk of fractures. Osteoporotic-related fractures increase morbidity and mortality and impair quality of life. Therefore, a correct approach for fracture prevention seems mandatory. Lifestyle changes should be recommended to all patients, including weight reduction if patients are obese/overweight, increasing physical activity and avoiding alcohol consumption and smoking. Additionally, calcium and vitamin D3 should be prescribed until the vitamin D deficit is resolved. Osteoporosis treatment options mainly include antiresorptives (i.e. estrogens, selective estrogen receptor modulators, bisphosphonates, denosumab) and anabolic agents (i.e. teriparatide, abaloparatide, romosozumab). Although presenting differences in efficacy and side effects, they have all been shown to increase bone mineral density (BMD) and to reduce osteoporotic-related fractures. Monotherapy with antiresorptive agents, particularly oral bisphosphonates, should be considered routinely as the first option for treatment of postmenopausal women. However, in the case of side effects, therapeutic failure or the need for long-term use, anabolic agents may be considered. In high-risk patients, anabolic agents may be considered as an initial therapeutic option. The combination of antiresorptive and anabolic agents may be useful to increase BMD compared with monotherapy, but more information is warranted to determine the effects on fracture risk.

Therapy to activate bone formation is required to reverse and restore the damaged bone architecture found in women with postmenopausal osteoporosis. The osteoanabolic drugs include teriparatide, which has been available for several years, and abaloparatide and romosozumab, novel osteoanabolic drugs that have become available more recently. By stimulating bone formation, these drugs produce greater increases in bone mass and bone strength, and they do so more quickly compared to the commonly used anti-remodeling (also called antiresorptive) drugs such as bisphosphonates. In head-to-head trials, teriparatide and romosozumab reduce fracture risk more effectively than do oral bisphosphonates in women with osteoporosis and high fracture risk. Osteoanabolic drugs have little role in the prevention of bone loss during early menopause, but they have an important place in the treatment of women at very high risk of fracture or who remain at high fracture risk after a course of bisphosphonate therapy. Primarily because of the high cost of the drugs, these therapies are initiated by specialists rather than primary-care physicians in most countries. This review will present the evidence for efficacy and safety of these drugs so that clinicians may discern their appropriate use when caring for postmenopausal women with osteoporosis.

The aim of this study was to investigate the effect and timing of recombinant human parathyroid hormone analog (PTH) administration for preventing medication-related osteonecrosis of the jaws (MRONJ) using a murine model. After standardized MRONJ induction using zoledronic acid and dexamethasone injections, 48 female Sprague-Dawley rats were divided into four groups according to the timing of PTH administration before or after dental extraction. Rats were euthanized 3 weeks after dental extraction, followed by clinical and histologic analyses. No clinical improvements were observed in the preoperative and postoperative PTH groups, compared to controls (p = 0.638 and 0.496, respectively). However, on histological analysis, the number of empty lacunae reduced significantly, and the number of blood vessels increased in the preoperative PTH group (p = 0.004 and 0.002, respectively). The postoperative PTH group did not show significant differences for empty lacunae and blood vessels compared to controls (p = 0.075 and 0.194, respectively). The reduction in the empty lacunae and the increase in the blood vessels in the preoperative PTH group were significant compared to other groups, suggesting more viable bone tissue in this group. In perspective, preoperative PTH use may represent a better prophylactic regimen for preventing the occurrence of MRONJ after traumatic dental or surgical procedures, especially in patients with a history of long-term bisphosphonate administration or at high risk of developing MRONJ. However, the findings should be proven in further studies on other animals followed by clinical trials.

Considering the lack of studies determining the real TPTD efficacy in individuals who develop MRONJ, our objective was to combine the available data on MRONJ cases treated with TPTD. The findings demonstrated that TPTD in combination with another therapy, especially antibiotic therapy, can be considered an effective protocol for MRONJ. To integrate the data published on the effect of teriparatide (TPTD) therapy on cases of medication-related osteonecrosis of the jaws (MRONJ) into a comprehensive analysis of clinical features. An electronic search was undertaken in six databases. Descriptive analyses of clinicodemographic data of MRONJ were carried out. Poisson regression was also run to evaluate predictors of total resolution of MRONJ treated with TPTD. Twenty-six publications comprising 111 cases were included. Most reported cases affected female individuals (82.0%) with a mean age of 76.54 years. Osteoporosis (76.5%) represented the main reason for using antiresorptive drugs, with bisphosphonates (98.1%) as the most frequently reported. Comorbidities were commonly present. The most related trigger factor of MRONJ was dental extraction (61.7%). Mandible (75.8%) was the most commonly affected site, with a mean evolution time of 5 months. MRONJ stage 2 (61.3%) was the most prevalent. Regarding TPTD treatment, in 45.1% cases, TPTD was used alone, with the total resolution being observed in 59.5% of the individuals. Associated therapy (54.9%) included surgery, antibiotic therapy, and laser therapy. Mean follow-up was 8.7 months. Poisson regression demonstrated that individuals with MRONJ stage 1 were 1.21 times more likely to present total resolution of osteonecrosis than individuals with MRONJ stage 3 (CI = 1.02–1.43; p

The treatment of large segmental defects of long bones resulting from trauma, infection, or bone tumor resections is a major challenge for orthopedic surgeons. The reconstruction of bone defects with acellular allografts can be used as an osteoconductive approach. However, devitalized allografts are associated with high rates of clinical failure as a result of poor intrinsic osteoinduction properties and a lack of further remodeling. Nevertheless, evidence suggests that due to its anabolic properties, teriparatide (PTH1-34) could be effective as an adjuvant therapy for massive allograft healing. Therefore, our goal was to investigate in a murine critical-sized defect model whether the intermittent administration of PTH1-34 improves the incorporation and revitalization of acellular structural bone allografts. Thus, a 2.5-mm critical-sized defect was established in the right femur of C57BL/6 mice, followed by the reconstruction with a devitalized cortical structural allograft. A titanium micro locking plate was applied to the anterior femoral surface and secured in place with self-tapping locking screws. Subsequently, daily doses of PTH1–34 (30, and 40 µg/kg) or saline were administered to the mice for 14 days after surgery. The mice were maintained without PTH1–34 therapy for an additional 7 days before being euthanized at 3 weeks post-surgery. Bone graft consolidation was assessed on radiographic images and by histomorphometric analysis. Additionally, to determine the frequency of osteoprogenitor cells in the bone marrow and their in vitro osteogenic capacity, stromal cells were isolated from the bone marrow of animals treated with 30 or 40 µg/kg/day of PTH1-34 following the same protocol used for the experimental animals. Our results suggest that intermittent PTH1-34 treatment at 30 µg/kg/day after femoral allograft reconstruction surgery accelerated the healing process as evidenced by new bone formation induced on endosteal and periosteal surfaces, enhanced revitalization of allogeneic graft, and increased frequency and osteogenic capacity of bone marrow stromal cells (BMSC). These findings should encourage further studies aimed at investigating the potential therapeutic use of intermittent PTH1-34, specifically with regards to the optimal dosing regimen in clinically challenging orthopedic scenarios.

Pregnancy- and lactation-associated osteoporosis (PLO) is a rare disease, presenting in most cases with severe back pain due to low energy vertebral fractures (VFs). Our purpose was to assess the effect of teriparatide (TPTD) vs. conventional management on areal bone mineral density (aBMD) and trabecular bone score (TBS) in patients with PLO. A multicenter retrospective cohort study concerning premenopausal women with PLO. Nineteen women were treated with TPTD (20 μg/day) (group A) plus calcium and vitamin D and eight women with calcium and vitamin D only (group B) for up to 24 months. The primary end-point was between group differences in lumbar spine (LS) and total hip (TH) aBMD, and TBS at 12 and 24 months. Patients in group A had sustained a median of 4.0 VFs (3–9) vs. 2.5 VFs (1–10) in group B (p = 0.02). At 12 months, patients on TPTD vs. controls achieved a mean aBMD increase of 20.9 ± 11.9% vs. 6.2 ± 4.8% at the LS (p

Medication-related osteonecrosis of the jaw (MRONJ) is a severe adverse reaction experienced by some individuals to certain medicines commonly used in the treatment of cancer and osteoporosis (e.g. bisphosphonates, denosumab, and antiangiogenic agents), and involves the progressive destruction of bone in the mandible or maxilla. Depending on the drug, its dosage, and the duration of exposure, this adverse drug reaction may occur rarely (e.g. following the oral administration of bisphosphonate or denosumab treatments for osteoporosis, or antiangiogenic agent-targeted cancer treatment), or commonly (e.g. following intravenous bisphosphonate for cancer treatment). MRONJ is associated with significant morbidity, adversely affects quality of life (QoL), and is challenging to treat. This is an update of our review first published in 2017.To assess the effects of interventions versus no treatment, placebo, or an active control for the prophylaxis of MRONJ in people exposed to antiresorptive or antiangiogenic drugs. To assess the effects of non-surgical or surgical interventions (either singly or in combination) versus no treatment, placebo, or an active control for the treatment of people with manifest MRONJ.Cochrane Oral Health's Information Specialist searched four bibliographic databases up to 16 June 2021 and used additional search methods to identify published, unpublished, and ongoing studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing one modality of intervention with another for the prevention or treatment of MRONJ. For 'prophylaxis of MRONJ', the primary outcome of interest was the incidence of MRONJ; secondary outcomes were QoL, time-to-event, and rate of complications and side effects of the intervention. For 'treatment of established MRONJ', the primary outcome of interest was healing of MRONJ; secondary outcomes were QoL, recurrence, and rate of complications and side effects of the intervention.Two review authors independently screened the search results, extracted the data, and assessed the risk of bias in the included studies. For dichotomous outcomes, we reported the risk ratio (RR) (or rate ratio) and 95% confidence intervals (CIs).We included 13 RCTs (1668 participants) in this updated review, of which eight were new additions. The studies were clinically diverse and examined very different interventions, so meta-analyses could not be performed. We have low or very low certainty about available evidence on interventions for the prophylaxis or treatment of MRONJ. Prophylaxis of MRONJ Five RCTs examined different interventions to prevent the occurrence of MRONJ. One RCT compared standard care with regular dental examinations at three-month intervals and preventive treatments (including antibiotics before dental extractions and the use of techniques for wound closure that avoid exposure and contamination of bone) in men with metastatic prostate cancer treated with zoledronic acid. The intervention seemed to lower the risk of MRONJ (RR 0.10, 95% CI 0.02 to 0.39, 253 participants). Secondary outcomes were not evaluated. Dentoalveolar surgery is considered a common predisposing event for developing MRONJ and five RCTs tested various preventive measures to reduce the risk of postoperative MRONJ. The studies evaluated plasma rich in growth factors inserted into the postextraction alveolus in addition to standardised medical and surgical care versus standardised medical and surgical care alone (RR 0.08, 95% CI 0.00 to 1.51, 176 participants); delicate surgery and closure by primary intention versus non-traumatic tooth avulsion and closure by secondary intention (no case of postoperative MRONJ in either group); primary closure of the extraction socket with a mucoperiosteal flap versus application of platelet-rich fibrin without primary wound closure (no case of postoperative MRONJ in either group); and subperiosteal wound closure versus epiperiosteal wound closure (RR 0.09, 95% CI 0.00 to 1.56, 132 participants). Treatment of MRONJ Eight RCTs examined different interventions for the treatment of established MRONJ; that is, the effect on MRONJ cure rates. One RCT analysed hyperbaric oxygen (HBO) treatment used in addition to standard care (antiseptic rinses, antibiotics, and surgery) compared with standard care alone (at last follow-up: RR 1.56, 95% CI 0.77 to 3.18, 46 participants). Healing rates from MRONJ were not significantly different between autofluorescence-guided bone surgery and conventional bone surgery (RR 1.08, 95% CI 0.85 to 1.37, 30 participants). Another RCT that compared autofluorescence- with tetracycline fluorescence-guided sequestrectomy for the surgical treatment of MRONJ found no significant difference (at one-year follow-up: RR 1.05, 95% CI 0.86 to 1.30, 34 participants). Three RCTs investigated the effect of growth factors and autologous platelet concentrates on healing rates of MRONJ: platelet-rich fibrin after bone surgery versus surgery alone (RR 1.05, 95% CI 0.90 to 1.22, 47 participants), bone morphogenetic protein-2 together with platelet-rich fibrin versus platelet-rich fibrin alone (RR 1.10, 95% CI 0.94 to 1.29, 55 participants), and concentrated growth factor and primary wound closure versus primary wound closure only (RR 1.38, 95% CI 0.81 to 2.34, 28 participants). Two RCTs focused on pharmacological treatment with teriparatide: teriparatide 20 μg daily versus placebo in addition to standard care (RR 0.96, 95% CI 0.31 to 2.95, 33 participants) and teriparatide 56.5 μg weekly versus teriparatide 20 μg daily in addition to standard care (RR 1.60, 95% CI 0.25 to 1.44, 12 participants).Prophylaxis of medication-related osteonecrosis of the jaw One open-label RCT provided some evidence that dental examinations at three-month intervals and preventive treatments may be more effective than standard care for reducing the incidence of medication-related osteonecrosis of the jaw (MRONJ) in individuals taking intravenous bisphosphonates for advanced cancer. We assessed the certainty of the evidence to be very low. There is insufficient evidence to either claim or refute a benefit of the interventions tested for prophylaxis of MRONJ in patients with antiresorptive therapy undergoing dentoalveolar surgery. Although some interventions suggested a potential large effect, the studies were underpowered to show statistical significance, and replication of the results in larger studies is pending. Treatment of medication-related osteonecrosis of the jaw The available evidence is insufficient to either claim or refute a benefit, in addition to standard care, of any of the interventions studied for the treatment of MRONJ.

Pregnancy- and lactation-associated osteoporosis (PLO) is a rare and severe disorder that causes low-trauma or spontaneous fractures, most commonly multiple vertebral fractures, in the late pregnancy or lactation period [1]. In severe PLO, teriparatide (TPTD) might aid in bone mineral density (BMD) recovery and subsequent fracture risk reduction. However, it is unclear whether TPTD can be discontinued without sequential antiresorptive therapy (ART) in premenopausal women with PLO. In this retrospective cohort study, we investigated the changes in BMD in premenopausal women with PLO treated with TPTD 20 mcg daily with or without sequential ART. Data for 67 patients diagnosed with PLO from 2007 through 2017 were reviewed. Among 43 women with annual follow-up dual-energy X-ray absorptiometry data for 3 years, 33 were treated with TPTD (median 12 months) with (TPTD-ART, n = 13; median, 18 months) or without (TPTD-no ART, n = 20) sequential ART. The two groups showed no differences in the mean age (31 vs. 31 years), body mass index (BMI, 20.5 vs. 21.0 kg/m2), and baseline lumbar spine (LS) BMD (0.666 vs. 0.707 g/cm2; p > 0.05 for all). LSBMD increased at 1, 2, and 3 years from baseline in both the TPTD-ART (14.1%, 21.8%, and 24.0%, respectively) and TPTD-no ART (17.3%, 24.1%, and 23.4%, respectively) groups, without significant between-group differences. Similar results were observed for the total hip BMD. LSBMD gain at 3 years did not differ by ART use (adjusted β, 0.40; p = 0.874) in univariable and multivariable models adjusted for age, BMI, and baseline LSBMD. In summary, BMD gain by TPTD administration in premenopausal women with PLO can be well maintained without sequential ART treatment.

Objective: The objective of this meta-analysis was to compare the efficacy and safety of teriparatide versus salmon calcitonin for the treatment of osteoporosis in Asian patients and to investigate whether the results of global studies could be applicable to Asian patients. Methods: PubMed, OVID, Cochrane Central Register of Controlled Trials (CENTRAL) and EMBASE up to December 2018 were searched. Eligible randomized controlled trials (RCTs) that compared teriparatide versus salmon calcitonin in Asian osteoporosis population were included. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used for data synthesis, and Cochrane Collaboration software Review Manager 5.3 was used to analyze the pooled data. Results: Three RCTs involving 529 patients were included (mean age 68.7 yr; 93.4% females; mean follow-up 6 months); outcome measures included bone mineral density (BMD) of the femoral neck, total hip and lumbar spine; bone markers and adverse events. We found that the period of 6-months of teriparatide treatment was helpful for the improvement of the BMD of lumbar vertebra, however, the improvement of BMD was not significant in the femoral neck and total hip joint. There was a positive correlation between bone-specific alkaline phosphatase (BSAP) and osteocalcin (OCN) and the response of Asian patients to subcutaneous injection of 20 micrograms per day of teriparatide. The proportion of the occurrence of adverse effects was more obvious in the teriparatide group compared with salmon calcitonin, but there was no significant difference. Conclusion: Results suggested that the use of teriparatide could improve the lumbar BMD by shortterm (six months) application in Asian osteoporosis patients, which is beneficial to the patients who cannot tolerate adverse events of long-term treatment. The BSAP and OCN bone markers could be useful to monitor the responses of Asian osteoporosis patients to teriparatide treatment. Finally, both of teriparatide and salmon calcitonin were well tolerated by Asian patients.

Atypical femur fracture (AFF) is an uncommon complication of long-term bisphosphonate use, but the risk declines substantially after treatment cessation. We report a case of a 70-year-old woman with osteopenia treated with alendronate for 9 years who presented with right mid-thigh pain and radiographic findings of focal lateral cortical thickening in the right mid-femur and lateral cortex irregularity in the proximal-mid left femur. Alendronate was discontinued, but she remained on estrogen for menopausal symptoms. Four years later, a horizontal linear translucent defect was seen in the right mid-femur area of cortical hypertrophy, consistent with an incomplete AFF. The patient underwent prophylactic intramedullary rodding of the right femur and estrogen was discontinued. Three years later (7 years after initial presentation), the cortical irregularities in the left femur were more prominent and three small horizontal linear translucent defects were now evident, consistent with early incomplete atypical fracture development. The patient also suffered a wrist fracture. She was treated with teriparatide for 1.5 years with resolution of the translucent defects in the left but not the right femur, although abnormal thickening of the lateral cortex persisted in both femurs. Our case demonstrates incomplete atypical femur fracture progression in a patient with long-term bisphosphonate exposure, even after treatment cessation. These findings highlight the importance of follow-up for patients who develop diaphyseal femur stress fractures and the potential for early healing with anabolic therapy. This case also demonstrates the challenge in managing older patients with incomplete AFF at risk for progression to complete AFF and osteoporotic fracture.

Objective To compare the preventive effects of teriparatide and alendronate on the progression of vertebral body collapse in postmenopausal single‐level Kümmell's disease (KD). Methods From March 2013 to December 2020, the medical records for 53 postmenopausal single‐level KD patients who received conservative treatment with teriparatide (25 patients, teriparatide group) or alendronate (28 patients, alendronate group) were retrospectively reviewed. Midsagittal computed tomography (CT) images were analyzed by ImageJ to assess the intravertebral bone formation (mineralized bone) by calculating the ratio of area of intravertebral mineralized bone (AIMB) to the area of fractured vertebral body (AFVB). The changes in radiological parameters of the fractured vertebral body including kyphosis angle (KA), anterior and posterior border heights (ABH and PBH) and spinal canal diameter (SCD), bone turnover biomarkers (BTMs), and bone mineral density (BMD) were analyzed to evaluate the therapeutic effect. Results At month 12, the ratio of AIMB to AFVB was significantly greater in teriparatide group (54.28% ± 15.30%) than in alendronate group (35.57% ± 17.61%) (P, Illustrating the KD diagnosis. The hyperintensity detected on sagittal T2‐weighted MR images (A) and fat‐suppressed sequence (B) within T12 for an 84‐year‐old patient or the gas‐containing cleft detected on the CT scan (C) with T10 for a 69‐year‐old patient demonstrates the formation of intravertebral vacuum cleft (arrows), indicating KD. KD Kümmell's disease.

Background Osteoporotic vertebral compression fracture (OVCF) is a common disease in elderly population, which could cause serious back pain and has a substantial impact on patients' health-related quality of life (HRQoL). The aim of this study was to identify the effect of Teriparatide as a conservative treatment on reducing back pain, and improving quality of life for postmenopausal women with osteoporotic vertebral fractures. Methods In a 12-month, retrospective study, 112 postmenopausal women with OVCFs were assigned to Teriparatide group (20 µg Teriparatide, subcutaneous, once daily, n=38) or control group (500 mg calcium and 400-800 IU Vitamin D per day, oral administration, n=74) according to patients' choices between January 2016 and October 2018. Patient-reported outcomes scores including the visual analogue score (VAS), Oswestry disability index (ODI), and short form 36 questionnaire (SF-36) were assessed at baseline, the 3rd months, the 6th months and 1 year after treatment. Results Treatments with Teriparatide or calcium plus vitamin D supplements had significant effect on improvement of patients' back pain as well as HRQoL, with significantly reduced VAS and ODI and increased SF-36 physical component summary (PCS) and mental component summary (MCS) scores. At the endpoint, Teriparatide showed better therapeutic effect, with greater reductions in VAS and ODI and more increases in SF-36 PCS and MCS scores. However, more adverse events (AEs) were found in Teriparatide group, but symptoms were relatively mild and of short duration. Conclusions In postmenopausal women with OVCFs, the consequent persistent back pain and impaired HRQoL, treatment with Teriparatide was associated with more profound therapeutic effects and more AEs compared with calcium plus vitamin D supplements.

Medication-related osteonecrosis of the jaw (MRONJ) is a complex disease which can be associated with multiple morbidities and is challenging to treat. This review evaluates the literature on the role and efficacy of teriparatide (TPTD) as a treatment for MRONJ. The clinical, radiological, histopathological and serological parameters used to assess treatment response have been described. Electronic databases were searched to retrieve articles (April 2005 and April 2020) based on strict inclusion criteria. Seventeen articles were included in this review. Of the 91 patients treated; only six received TPTD as a standalone treatment. There were significant variations in defining treatment outcomes and measuring treatment response. The longest follow-up period was 26 months, and 12 studies failed to report follow-up. The overall quality of evidence is weak with potential for a high risk of bias, making it difficult to determine the efficacy of TPTD and its long-term effects. However, TPTD may play a role in the treatment of intractable MRONJ in osteoporotic patients or those unfit for surgery. Therefore, randomized clinical trials on larger patient cohorts with long-term follow-up is required to confirm efficacy, safety and inform treatment indications for TPTD in the treatment of MRONJ.

The development of coronavirus disease 2019 (COVID‐19) vaccines has proceeded at an unprecedented pace, with numerous trials conducted simultaneously across the world as a result of massive technological and financial resource expenditures. With multiple vaccines having now received regulatory approval, public health efforts to promote widespread vaccine dissemination are currently underway. There has been particular emphasis placed on vaccination of older populations, the age group in which COVID‐19 infection has been most lethal. However, such widespread vaccination approaches have necessarily raised important questions related to potential interactions with underlying diseases and concomitant treatments among persons to be vaccinated. Osteoporosis is a chronic condition marked by reduced bone strength and an associated increased risk for fracture that generally requires sustained medical intervention(s). Osteoporosis is neither associated with a higher risk of COVID‐19 infection nor by more pronounced disease severity following infection, such that individuals with osteoporosis need not be more highly prioritized for COVID‐19 vaccination. Osteoporosis therapies do not interfere with the efficacy or side effect profiles of COVID‐19 vaccines and should not be stopped or indefinitely delayed because of vaccination. Depending on the specific drug profile within an anti‐osteoporosis medication category, minor adjustments to the timing of drug administration may be considered with respect to the patient's COVID‐19 vaccination schedule. Herein we provide practical recommendations for the care of patients requiring treatment for osteoporosis in the setting of COVID‐19 vaccination. © 2021 American Society for Bone and Mineral Research (ASBMR).

The state of the art of osteoporosis management and treatment is being continuously refined according to recent progress in data availability, drug development and strategies as determined by health authorities. The recent approval of the sclerostin-antibody romosozumab as a novel first in class anabolic drug is another milestone that enriches our therapeutic portfolio. Neutralisation of the wnt-pathway inhibitor sclerostin by romosozumab leads to rapid stimulation of bone formation and a rise in bone mineral density that translates into robust 70 % reduction of fracture risk at the lumbar spine. Already after one year of treatment romosozumab is stopped and followed by antiresorptive maintenance treatment. The indication for this strategy is severe osteoanabolic compounds can now be applied as a first line treatment without prior antiresorptive medication. The new data helped in alleviating restrictions by the authorities for first line use of anabolic strategies. Romosozumab and teriparatide represent two anabolic strategies that differ in their mode of action although the molecular mechanisms are partially overlapping. Teriparatide is primarily active as a remodeling agent whereas romosozumab exerts bone mass gains mainly via modeling. Differential therapeutic strategies throughout a patient "career" may take into account these differences as well as adverse effects and individual contraindications. Based on all our recent progress and achievement we can more and more individualize the long term management of osteoporosis over decades applying an individual "treat to target" strategy. Basically, osteoporosis is a chronic disease and has to be treated as such. If however for whatever reason treatment regimens using biologicals are being discontinued we have to be aware that such situations need to be stabilized using long-acting bisphosphonates to maintain the therapeutic success and avoid rapid bone loss and fracture risk.Romosozumab ist ein humanisierter Antikörper gegen das Osteozyten-spezifische Protein Sklerostin. Die Neutralisierung von Sklerostin mit Romosozumab fördert die Knochenneubildung. Die schnelle Zunahme an Knochenmasse reduziert deutlich das Frakturrisiko und geht bereits nach einem Jahr in ein Plateau über. Als Erhaltungstherapie ist eine anschließende antiresorptive Therapie erforderlich. Romosozumab ist zugelassen als neues anaboles Wirkprinzip für die Behandlung der schweren Osteoporose. Es besteht ein Warnhinweis für kardiovaskuläre Erkrankungen wie Myokardinfarkt oder Schlaganfall in den letzten 12 Monaten. PRIMäR ANABOLE THERAPIE: Nach Aufhebung des G-BA-Therapiehinweises zu Teriparatid mit dem 06.04.2019 ist eine primär anabole Therapie der Osteoporose ohne vorherige antiresorptive Behandlung möglich. Das Vorgehen sollte individualisiert an die Krankheitsaktivität und das Frakturrisiko angepasst werden. Die anabole Therapie erfolgt mit Romosozumab oder Teriparatid, jeweils gefolgt von einer Erhaltungstherapie mit einem Antiresorptivum. Eine primär antiresorptive Behandlung ist unverändert sinnvoll bei ausreichend erhaltener Knochenstruktur und hohem Verlust-/Frakturrisiko.Leitliniengerechte individualisierte Langzeitkonzepte müssen dem persönlichen Risikoprofil und der Krankheitsaktivität gerecht werden. Behandlungsziele („treat to target“) sind die funktionelle Wiederherstellung auf das Niveau vor Fraktur(en) und die bestmögliche Reduktion des zukünftigen Frakturrisikos. Die Langzeittherapie besteht aus sinnvollen Sequenzen, eine lebenslange Therapie mit einem einzigen Medikament ist nicht durchführbar.

Summary This study assessed the cost effectiveness of romosozumab versus teriparatide, both sequenced to alendronate, for the treatment of severe postmenopausal osteoporosis in Japan, using bone mineral density (BMD) efficacy data. Results show that romosozumab/alendronate produces greater health benefits at a lower cost than teriparatide/alendronate. Introduction This study aims to assess the cost effectiveness of romosozumab versus teriparatide, both sequenced to alendronate, for the treatment of severe postmenopausal osteoporosis in Japanese women previously treated with bisphosphonates. Methods A Markov model was used to assess the relative cost effectiveness of 1 year of romosozumab versus 2 years of teriparatide, both sequenced to alendronate for a total treatment duration of 5 years. Outcomes for a cohort of women with a mean age of 78 years, a T-score ≤−2.5 and a previous fragility fracture were simulated over a lifetime horizon. The analysis was conducted from the perspective of the Japanese healthcare system and used a discount rate of 2% per annum. To inform relative fracture incidence, the bone mineral density (BMD) advantage of romosozumab over teriparatide was translated into relative risks of fracture, using relationships provided by a meta-regression of osteoporosis therapy trials. Outcomes were assessed in terms of lifetime costs (2020 US dollars) and quality-adjusted life years (QALYs). Results Base case results showed that, compared with teriparatide/alendronate, romosozumab/alendronate reduced costs by $5134 per patient and yielded 0.045 additional QALYs. Scenario analyses and probabilistic sensitivity analysis confirmed that results are robust to uncertainty in model assumptions and inputs. Conclusion Results show that romosozumab/alendronate produces greater health benefits at a lower total cost than teriparatide/alendronate.

Long-term glucocorticoid (GC) therapy is frequently indicated to treat autoimmune and chronic inflammatory diseases in daily clinical practice. Two of the most devastating untoward effects are bone loss and fractures. Doses as low as 2.5 mg of prednisone for more than 3 months can impair bone integrity. Population at risk is defined based on the dose and duration of GC therapy and should be stratified according to FRAX (Fracture Risk Assessment Tool), major osteoporotic fracture, prior fractures, and bone mineral density values (BMD). General measures include to prescribe the lowest dose of GC to control the underlying disease for the shortest possible time, maintain adequate vitamin D levels and calcium intake, maintain mobility, and prescribe a bone acting agent in patients at high risk of fracture. These agents include oral and intravenous bisphosphonates, denosumab, and teriparatide.

Patients with anorexia nervosa (AN) often experience low bone mineral density (BMD) and increased fracture risk, with low body weight and decreased gonadal function being the strongest predictors of the observed bone mineral deficit and fractures. Other metabolic disturbances have also been linked to bone loss in this group of patients, including growth hormone resistance, low insulin-like growth factor-1 (IGF-1) concentrations, low leptin concentrations, and hypercortisolemia. However, these correlations lack definitive evidence of causality. Weight restoration and resumption of menstrual function have the strongest impact on increasing BMD. Other potential treatment options include bisphosphonates and teriparatide, supported by data from small clinical trials, but these agents are not approved for the treatment of low BMD in adolescents or premenopausal women with AN.

The aim of this scoping review was to summarise current knowledge about the effects of bone anabolic drugs on periodontitis, in order to identify new therapeutic strategies for preventing disease progression and reducing tooth loss. A technical expert panel (TEP) was established of 11 medical specialists, including periodontists and bone specialists that followed the PRISMA-ScR model to perform the scoping review and considered for eligibility both pre-clinical and clinical studies published in the English language up to September 2020. 716 items were initially found. After duplicate removal and screening of articles for eligibility criteria, 25 articles published between 2001 and 2019 were selected. Only studies concerning teriparatide, strontium ranelate, sclerostin antibodies and DKK1 antibodies met the eligibility criteria. In particular, only for teriparatide were there both clinical studies and experimental studies available, while for other bone anabolic drugs only animal studies were found. Available evidence about the use of bone anabolic drugs in periodontology demonstrates beneficial effects of these agents on biological pathways and histological parameters involved in periodontal tissue regeneration that suggest relevant clinical implications for the management of periodontitis.

Objectives: The objective of this study was to evaluate and compare the efficacy of teriparatide (osteoanabolic agent) versus vitamin D3 supplementation to improve functional outcomes in osteoporotic patients with distal end radius fractures (DERF). Methods: We conducted a prospective, randomized clinical study to compare the functional outcomes. Sixty osteoporotic DERF patients, treated with either conservative or surgical management were randomized to receive either teriparatide (20 mcg/day) or vitamin D3 (1000 IU/day) for a period of 3 months, along with calcium (500 mg/day) supplementation. The treatment outcomes were evaluated pre and post-management (1-month and 3-months) by Green and O’Brien scale, Patient-rated Wrist Evaluation (PRWE) scale, and Sarmiento scale. Results: There was a significant difference between the two groups at 3-months post-management. Teriparatide showed a significantly greater improvement of functional outcome (P=0.036) and patient-reported outcome (P

MicroRNAs regulate bone homeostasis, and circulating microRNAs have been proposed as novel bone biomarkers. The effect of anti‐osteoporotic treatment on circulating microRNAs has not been described in detail. Therefore, we performed a comprehensive analysis of microRNA serum levels in ovariectomized (OVX) and sham‐operated (SHAM) rats over 12 weeks of antiresorptive or osteoanabolic treatment. Forty‐two Sprague Dawley rats underwent SHAM surgery (n = 10) or ovariectomy (n = 32). After 8 weeks, OVX rats were randomized to antiresorptive treatment with zoledronate (n = 11), osteoanabolic treatment with teriparatide (n = 11), or vehicle treatment (n = 10). Serum samples were collected at weeks 8, 12, 16, and 20 after surgery. A total of 91 microRNAs were analyzed by RT‐qPCR in serum samples collected at week 20. Based on the results, 29 microRNAs were selected for longitudinal analysis at all four study time points. Changes in bone mineral density and microstructure were followed up by in vivo micro‐CT and ex vivo nano‐CT. Ovariectomy resulted in the loss of trabecular bone, which was reversed by osteoanabolic and antiresorptive treatment. Differential expression analysis identified 11 circulating miRNAs that were significantly regulated after treatment. For example, miR‐107 and miR‐31‐5p increased in vehicle‐treated OVX animals, whereas they decreased during teriparatide treatment. Additional miRNAs were identified that showed significant correlations to bone microstructure or bone miRNA expression, including miR‐203a‐3p, which exhibited a significant negative correlation to vertebral and tibial trabecular bone volume fraction (%). Longitudinal analysis confirmed eight microRNAs with significant changes in serum over time that were prevented by teriparatide and zoledronate treatment (miR‐34a‐5p, miR‐31‐5p, miR‐30d‐3p, miR‐378a‐5p) or teriparatide treatment only (miR‐375‐3p, miR‐183‐5p, miR‐203a‐3p, miR‐203b‐3p). Gene target network analysis identified WNT and Notch signaling as the main signaling pathways controlled by these miRNAs. Thus, ovariectomy results in time‐dependent deregulation of circulating miRNAs compared with SHAM animals. Anti‐osteoporotic treatments can rescue this effect, showing that bone‐related miRNAs might act as novel biomarkers for treatment monitoring. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Objectives To assess differences in efficacy of a 28.2-μg teriparatide formulation for twice-weekly use (2/W-TPTD) by patient characteristics. Methods A post hoc analysis was performed using data from a multicenter, randomized, double-blind, double-dummy, non-inferiority trial (TWICE study) conducted in Japan comparing the efficacies of once-weekly and twice-weekly injections of teriparatide (TPTD). Specifically, a stratified analysis of percentage changes from baseline was performed using the final data on lumbar spine bone mineral density (BMD) after a 48-week treatment period (n = 251, 2/W-TPTD; n = 239, a 56.5-μg teriparatide formulation for once-weekly use [1/W-TPTD]). Results Across all subgroups defined by patient characteristics that included 9 or more subjects, the lumbar spine BMD increased significantly in both groups. In the 2/W-TPTD group, the percentage change was significantly higher in subjects with no non-vertebral fractures without large external force occurring at or after age 50 years versus those with such fractures. The lower the stratification in baseline lumbar spine BMD, total hip BMD, or femoral neck BMD, the greater was the percentage change. Conclusions Whereas all subgroups can expect a significant improvement in lumbar spine BMD, there were some patient characteristics that affected the percentage increase in BMD.

Objective: The objective of the study was to show the efficacy of teriparatide in comminuted fracture healing and improvement in overall functional recovery. Methods: A total of 30 subjects who suffered from comminuted fractures of lower limb were selected. Subjects were categorized into two groups: Group A (n=15) contained individuals with teriparatide administration and Group B (n=15) contained individuals who were not administered teriparatide. 20 mg of teriparatide was injected subcutaneously for a period of 3 months. Patients were followed up ay durations of 4, 8, and 12 weeks. Obtained data were entered into Microsoft Excel Worksheets and descriptive analysis was performed. Chi-square test was used to analyze all obtained data. Results: Among Group A patients, the fracture healing rates were found to be significantly earlier with comparison to control group (Group B). Conclusion: Teriparatide was observed to be effective in comminuted fracture healing and has demonstrated good clinical outcome.

Background.Non-adherence to treatment, especially in chronic conditions, is a significant problem facing clinical medicine. Failure to adhere to treatment recommendations is often noted in the treatment of osteoporosis, which reduces the effectiveness of anti-osteoporotic drugs and a set of measures to prevent the occurrence of osteoporotic fractures.Aim. The aim of the study was to assess the adherence of patients of the Center for the Prevention and Treatment of Osteoporosis to treatment with anti-osteoporotic drugs of pathogenetic action.Materials and methods.This continuous observational study analyzed the adherence to long-term anti-osteoporotic therapy of patients observed at the Center for the Prevention and Treatment of Osteoporosis, the reasons for discontinuing treatment, doctors’ preferences in prescribing anti-osteoporotic therapy, reasons for changing the anti-osteoporotic drug. The study period is from July to December 2019.Results.During the analyzed period, 625 patients turned to the Center for the Prevention and Treatment of Osteoporosis. The preferences of doctors when prescribing anti-osteoporotic therapy have changed: the proportion of prescriptions for zoledronic acid and denosumab increased, mainly due to a reduction in the prescriptions of strontium ranelate, as well as risendronic acid, teriparatide, and calcitonin was no longer prescribed. Among 370 patients who received a therapeutic appointment (with an already known outcome of a therapeutic appointment), 40.0 ± 2.5% were non-compliant. Including: 9.7 ± 1.5% did not start taking the drug, interrupted the course ahead of schedule — 28.7 ± 2.4%. The termination of the course of therapy in 57.7% of cases was unauthorized, in another 42.3% it was associated with side effects. Patients started and continued further therapy with the initially prescribed drug in 53.8% of cases. As expected, the best adherence rates were found for drugs with parenteral administration once a year (zoledronic acid).Conclusions.Comparative analysis of the prescriptions of the main drugs of the pathogenetic action of patients of the center for the prevention and treatment of osteoporosis showed low compliance.

There are now three anabolic agents available for the treatment of postmenopausal women at high risk for fracture. The purpose of this review is to supply a rationale to aid in determining which agent should be used in which clinical settings. Studies over the last decade have shown that anabolic agents produce faster and larger effects against fracture than antiresorptive agents. Furthermore, trials evaluating anabolic antiresorptive treatment sequences have shown that anabolic first treatment strategies produce the greatest benefits to bone density, particularly in the hip region. However, there are no head-to-head evaluations of the three anabolic therapies with fracture outcomes or bone density, and these studies are not likely to occur. How to decide which agent to use at which time in a woman’s life is unknown. We review the most significant clinical trials of anabolic agents which have assessed fracture, areal or volumetric bone density, microarchitecture, and/or bone strength, as well as information gleaned from histomorphometry studies to provide a rationale for consideration of one agent vs another in various clinical settings. There is no definitive answer to this question; all three agents increase bone strength and reduce fracture risk rapidly. Since the postmenopausal lifespan could be as long as 40–50 years, it is likely that very high-risk women will utilize different anabolic agents at different points in their lives.

Pregnancy-associated osteoporosis (PAO) is a rare condition of skeletal fragility affecting women in pregnancy or the postpartum period. During normal pregnancy and lactation, substantial changes in calcium metabolism and skeletal physiology occur in order to meet the demands of the developing foetus. Whilst these adaptations are reversible and generally of no clinical consequence for the mother, a small number of women will develop osteoporosis and suffer fragility fractures. Vertebral fractures occur most commonly in PAO and are often multiple. Due to the rarity of PAO, systematic study to date has been limited. Aetiology is poorly understood, but traditional osteoporosis risk factors and genetic factors are likely to play a role. A small number of cases may be due to an underlying metabolic bone disorder or monogenic condition. Management of PAO is challenging, due both to a poor evidence base and the fact that spontaneous improvement in BMD is known to occur once pregnancy and lactation are complete. Bisphosphonates, denosumab and teriparatide have all been used in individual patients, but the data supporting their use are currently limited.

Combined teriparatide and denosumab rapidly and substantially increases bone mineral density (BMD) at all anatomic sites. Discontinuation of denosumab however, results in high-turnover bone loss and increased fracture risk. The optimal way to prevent this bone loss remains undefined. This study is a preplanned extension of the DATA-HD study, where postmenopausal women with osteoporosis were randomized to receive 9 months of either 20 μg or 40 μg of teriparatide daily overlapping with denosumab (60 mg administered at months 3 and 9). At the completion of this 15-month study, women were invited to enroll in the DATA-HD Extension where they received a single dose of zoledronic acid (5 mg) 24 to 35 weeks after the last denosumab dose. Areal BMD and bone turnover markers were measured at month 27 and 42 (12 and 27 months after zoledronic acid, respectively) and spine and hip volumetric bone density by quantitative CT was measured at month 42. Fifty-three women enrolled in the DATA-HD Extension. At the femoral neck and total hip, the mean 5.6% and 5.1% gains in BMD achieved from month 0 to 15 were maintained both 12 and 27 months after zoledronic acid administration. At the spine, the mean 13.6% gain in BMD achieved from month 0 to 15 was maintained for the first 12 months but modestly decreased thereafter, resulting in a 3.0% reduction (95% CI, -4.0% to -2.0%, p < .0001) 27 months after zoledronic acid. The pattern of BMD changes between months 15 and 42 were qualitatively similar in the 20-μg and 40-μg groups. A single dose of zoledronic acid effectively maintains the large and rapid total hip and femoral neck BMD increases achieved with combination teriparatide/denosumab therapy for at least 27 months following the transition. Spine BMD was also largely, though not fully, maintained during this period. These data suggest that the DATA-HD Extension regimen may be an effective strategy in the long-term management of patients at high risk of fragility fracture. © 2021 American Society for Bone and Mineral Research (ASBMR).

Denosumab discontinuation is associated with rapid reversal of bone turnover suppression and with a considerable increase in fracture risk, including a risk for multiple vertebral fractures (MVF). Long-term follow-up of patients who sustained MVF after denosumab discontinuation has not been reported. This case-series was aimed to provide a long-term follow-up on the management and outcome of denosumab discontinuers who initially presented with multiple vertebral fractures. Denosumab discontinuers were identified from a computerized database of a large healthcare provider. Baseline and follow-up clinical, laboratory, and imaging data were obtained from the computerized database and electronic medical records. The post-denosumab discontinuers MVF patients consisted of 12 women aged 71±12. Osteoporotic fractures were prevalent before denosumab discontinuation in 6 of the patients. The majority received bisphosphonates before denosumab. MVF occurred 134±76 days after denosumab discontinuation. The patients were followed for a median of 36.5 (IQR 28.2, 42.5) months after MVF. Two patients passed-away. Two patients suffered recurrent vertebral fractures. Following MVF, patients were treated inconsistently with denosumab, teriparatide, oral, and intravenous bisphosphonates, in various sequences. Two patients underwent vertebroplasty/kyphoplasty. This long-term follow-up of real-world patients with MVF following denosumab discontinuation reveals that management is inconsistent, and recurrent fractures are not uncommon. It calls for clear management guidelines for patients with MVF after denosumab discontinuation and for special attention to this high-risk group.

Parathyroid hormone (PTH) and the paracrine factor, PTH-related protein (PTHrP), have preserved in evolution sufficient identities in their amino-terminal domains to share equivalent actions upon a common G protein-coupled receptor, PTH1R, that predominantly uses the cyclic adenosine monophosphate-protein kinase A signaling pathway. Such a relationship between a hormone and local factor poses questions about how their common receptor mediates pharmacological and physiological actions of the two. Mouse genetic studies show that PTHrP is essential for endochondral bone lengthening in the fetus and is essential for bone remodeling. In contrast, the main postnatal function of PTH is hormonal control of calcium homeostasis, with no evidence that PTHrP contributes. Pharmacologically, amino-terminal PTH and PTHrP peptides (teriparatide and abaloparatide) promote bone formation when administered by intermittent (daily) injection. This anabolic effect is remodeling-based with a lesser contribution from modeling. The apparent lesser potency of PTHrP than PTH peptides as skeletal anabolic agents could be explained by lesser bioavailability to PTH1R. By contrast, prolongation of PTH1R stimulation by excessive dosing or infusion, converts the response to a predominantly resorptive one by stimulating osteoclast formation. Physiologically, locally generated PTHrP is better equipped than the circulating hormone to regulate bone remodeling, which occurs asynchronously at widely distributed sites throughout the skeleton where it is needed to replace old or damaged bone. While it remains possible that PTH, circulating within a narrow concentration range, could contribute in some way to remodeling and modeling, its main physiological role is in regulating calcium homeostasis.