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Purpose: To analyze the available evidence and assess the effect of different implant coatings on healing outcomes. Materials and Methods: Using the PICOS strategy, a structured question was formed. A protocol was agreed upon and registered with PROSPERO (no. CRD42022321926). The MEDLINE, Embase, Cochrane Database of Systematic Reviews, Scopus, Web of Science, Pubmed, and ScienceDirect databases were searched using a structured strategy. Study selection was independently carried out in duplicate, first by title and abstract, then by full-text assessment. Quality and risk of bias were independently assessed in duplicate using AMSTAR 2 and ROBIS. Data extraction was independently undertaken in duplicate using a predefined extraction form. Results: The search yielded 11 systematic reviews for inclusion. The most commonly assessed coatings were based on calcium phosphate--including hydroxyapatite (HA), brushite, and bioabsorbable nano-HA--followed by bisphosphonate, then bioactive glass coatings. Included reviews most frequently assessed marginal bone loss (MBL), bone-to-implant contact (BIC), and survival/success rates. There was considerable heterogeneity and small sample sizes. The quality assessment suggested low confidence in the reviews and high risk of bias. Conclusions: The included reviews provide weak evidence that implant coatings improve osseointegration and reduce MBL following implant placement. There was weak evidence for progressive complications for calcium phosphate coatings. Further research and long-term multicenter controlled clinical trials with improved standardization and control of bias are required to better understand the effects of coating implants. [ABSTRACT FROM AUTHOR]

Objective: This paper aims to describe the 2023 update position paper on MRONJ developed by the Italian Societies of Oral Pathology and Medicine (SIPMO) and of Maxillofacial Surgery (SICMF). Methods: This is the second update following the 2013 and 2020 Italian position papers by the Expert panel, which is a representation of the two scientific societies (SIPMO and SICMF). The paper is based on an extensive analysis of the available literature from January 2003 to February 2020, and the subsequent review of literature conducted between March 2020 and December 2022 to include all new relevant published papers to confirm or modify the previous set of recommendations. Results: This position paper highlights the main issues of MRONJ on risk estimates, disease definition, diagnostic pathway, individual risk assessment, and the fundamental role of imaging in the diagnosis, classification, and management of MRONJ. Conclusion: The Expert Panel confirmed the MRONJ definition, the diagnostic work‐up, the clinical‐radiological staging system and the prophylactic drug holiday, as recognized by SIPMO‐SICMF; while, it presented novel indications regarding the categories at risk of MRONJ, the prevention strategies, and the treatment strategies associated with the therapeutic drug holiday. [ABSTRACT FROM AUTHOR]

Summary: Background: Falls and fractures are common and morbid for patients with cirrhosis. Bisphosphonates are recommended for the prevention of fractures for people with osteoporosis cirrhosis; however, data supporting effectiveness in cirrhosis are lacking. Aim: We sought to emulate a clinical trial of bisphosphonates in cirrhosis. Methods: We used national Medicare data (2008–2020) to examine the 5‐year risk of fractures in patients who did or did not receive bisphosphonates with a new‐user design among people diagnosed with cirrhosis and osteoporosis. We balanced treated and untreated with inverse probability of treatment weighting, evaluated intention‐to‐treat and as‐treated effects, and examined both control exposures (statin use) and outcomes (decompensation) to test causal relationships. Results: There were 253 and 20,888 new users and non‐users of bisphosphonates, respectively. The median age was 74 years. The most common bisphosphonate used was alendronate (73.6%). Bisphosphonates significantly reduced fractures overall (27.5% vs. 33.0%, p = 0.0004) in the intention‐to‐treat analysis, particularly for people <65 years (sHR 0.56) old, men (sHR 0.64) and those with non‐alcohol related liver disease (sHR 0.85). Though there were fewer arm (20.7% vs. 26.4%, p < 0.0001) and femur (28.9% vs. 31.2%, p = 0.005), there were more spinal (25.8% vs. 19.0%), rib (40.0% vs. 32.2%) and skull (10.1% vs. 8.7%) fractures. In the as‐treated analysis, cumulative bisphosphonate exposure significantly reduced fractures, sHR 0.95 95% CI (0.91, 0.98). Treatment was inconsistent; bisphosphonate users spent 29.9% person‐years of follow‐up on the drug. Conclusion: In a nationally representative cohort of elderly patients with cirrhosis, bisphosphonates reduced fractures overall. Efforts to increase uptake and drug continuation are needed. [ABSTRACT FROM AUTHOR]

Summary: Subtrochanteric femoral fracture is rare and intractable due to the possible association with low bone formation. Retrospective analysis of 38 patients with subtrochanteric femoral fractures revealed that four patients suffered from disorders related to low bone formation and there were specific treatments for two of them. Purpose: The main aim of this study was to detect latent metabolic bone diseases and skeletal dysplasia associated with low bone formation among patients with morphologic atypical femoral fracture (AFF). A second aim was to evaluate the frequency of recognized risk factors, such as antiresorptive agents, glucocorticoids, and age. Methods: Clinical information was retrospectively analyzed among 38 Japanese patients who were admitted to the Department of Orthopedic Surgery and Spinal Surgery and the Division of Emergency and Critical Care Medicine at the University of Tokyo Hospital with diagnoses of subtrochanteric fractures between February 2012 and March 2022. Results: Among 38 patients (including 30 females), 21 patients were aged 75 and over. Ten patients had past oral glucocorticoid use, and 18 had past antiresorptive agent use. Two patients were diagnosed with hypophosphatemic osteomalacia after the development of fractures. One patient was suspected to be a carrier of a loss-of-function variant of alkaline phosphatase, biomineralization associated (ALPL), and one other patient had previously been genetically diagnosed with pycnodysostosis. Among four patients with a diagnosis or suspicion of these metabolic bone diseases and skeletal dysplasia, four had past clinical fractures, two had past subtrochanteric femoral fractures, and two had subtrochanteric femoral fractures on both sides. Conclusion: If clinicians encounter patients with morphologic AFF, latent diseases related to low bone formation should be carefully differentiated because appropriate treatment may prevent delayed union and recurrent fractures. Additionally, it may be desirable to exclude these bone diseases in advance before initiating long-term use of antiresorptive agents in osteoporotic patients by screening with serum alkaline phosphatase levels to reduce the risk of morphologic AFF. [ABSTRACT FROM AUTHOR]

Summary: This multicentre, prospective cohort study measured the effect of romosozumab for 12 months on bone mineral density, taking into account prior therapies. Prior antiresorptive therapy blunted the BMD response to romosozumab, and the duration was correlated with BMD changes at both the lumbar spine and total hip. Introduction: In Switzerland, romosozumab is administered to high-risk osteoporosis patients. Our study aimed to assess the effect of romosozumab on bone mineral density (BMD), taking into account prior therapies. Methods: This multicentre, prospective cohort study measured the effect of romosozumab for 12 months in patients in a nationwide Swiss osteoporosis registry. BMD and bone turnover marker (P1NP and CTX) changes were measured and compared between pre-treated and treatment naïve patients. Results: Ninety-nine patients (92 women and 7 men, median age 71 years [65, 76]) were enrolled from January 2021 to December 2023. Among them, 22 had no prior treatment before romosozumab, while 77 had previous therapy (including 23 with a history of prior teriparatide therapy), with a median duration of 6 years [4, 11] of cumulative antiresorptive treatment. Over 12 months, romosozumab led to BMD changes of 10.3% [7.5, 15.5] at the lumbar spine, 3.1% [1.1, 5.8] at the total hip and 3.1% [0.5, 5.3] at the femoral neck, indicating notable variability. Significantly lower BMD responses were observed in pre-treated patients, with the duration of prior antiresorptive therapy inversely associated with BMD increases at the lumbar spine and hip. Other predictors of BMD changes at the total hip included baseline T-scores at the hip, body mass index and baseline CTX level, while the BMD response at the lumbar spine was associated with the lumbar spine T-score at baseline, age and baseline CTX level. Conclusion: Prior antiresorptive therapy blunted the BMD response to romosozumab, and the duration was correlated with BMD changes at both the lumbar spine and total hip. [ABSTRACT FROM AUTHOR]

Purpose: Tori and exostoses are considered risk factors for the development of medication-related osteonecrosis of the jaw (MRONJ). The aims of this study were to present the prevalence of MRONJ located at tori in the Copenhagen ONJ Cohort, evaluate the surgical treatment of MRONJ located at tori and explore trauma to tori as an additional risk factor in patients on antiresorptive medication. Methods: Data from a consecutive series of 506 patients with MRONJ (Copenhagen ONJ Cohort) were reviewed for the presence of tori and MRONJ located at tori. Demographic and medical data were analyzed, and healing outcomes and pain after the prophylactic removal of tori, surgical treatment of MRONJ located at tori, and conservative treatment of MRONJ located at tori were evaluated and compared using Fisher's exact test. Results: MRONJ located at tori was frequent and could be identified in 53% of the patients with tori, which accounts for a prevalence of 5.1% in the entire cohort. Of the 28 surgically treated patients, 27 (96.4%) healed uneventfully with no exposed bone after their first or second revision surgery. Fourteen (41.2%) patients with tori underwent therapeutic removal, eight (23.5%) underwent prophylactic removal, and six (17.6%) underwent both therapeutic and prophylactic removals. Two (33.3%) of the six conservatively treated patients healed spontaneously. Both treatment types resulted in a significant decrease in pain. Conclusion: Prophylactic and therapeutic surgical removal of tori are reliable treatments and should be considered if a patient's general health allows surgery. Trial registration: The study was approved by the Regional Scientific Ethical Committee (H-6–2013-010) on November 20, 2013, and was retrospectively registered. [ABSTRACT FROM AUTHOR]

Background: Medication-related osteonecrosis of the Jaw (MRONJ) is a rare but severe side effect in patients treated with medications such as Bisphosphonates (BPs). Its pathophysiological mechanism needs to be more precise. Establishing preventive measures and treatment standards is necessary. This study aimed to develop a composite hydrogel scaffold constituted by methacrylated gelatin (GelMA), methacrylated heparin (HepMA) and PRF, and investigate its potential application value in the prevention of MRONJ. Methods: GelMA, HepMA, and PRF were prepared using specific ratios for hydrogel scaffolds. Through mechanical properties and biocompatibility analysis, the release rate of growth factors and the ability to promote bone differentiation in vitro were evaluated. To explore the healing-enhancing effects of hydrogels in vivo, the composite hydrogel scaffold was implanted to the MRONJ rat model. Micro-computed tomography (Micro-CT) and histological examination were conducted to evaluate the bone morphology and tissue regeneration. Results: The Hep/GelMA-PRF hydrogel improved the degradation rate and swelling rate. It was also used to control the release rate of growth factors effectively. In vitro, the Hep/GelMA-PRF hydrogel was biocompatible and capable of reversing the inhibitory effect of zoledronic acid (ZOL) on the osteogenic differentiation of MC3T3-E1s. In vivo, the micro-CT analysis and histological evaluation demonstrated that the Hep/GelMA-PRF group exhibited the best tissue reconstruction. Moreover, compared to the ZOL group, the expression of osteogenesis proteins, including osteocalcin (OCN), type collagen I (Col I), and bone morphogenetic protein-2 (BMP-2) in the Hep/GelMA-PRF group were all significantly upregulated (P < 0.05). Conclusions: The Hep/GelMA-PRF hydrogel scaffold could effectively control the release rate of growth factors, induce osteogenic differentiation, reduce inflammation, and keep a stable microenvironment for tissue repair. It has potential application value in the prevention of MRONJ. [ABSTRACT FROM AUTHOR]

Osteoporosis and low bone mineral density (BMD) pose significant challenges in adult spinal deformity surgery, increasing the risks of complications such as vertebral compression fractures, hardware failure, proximal junctional kyphosis/failure, and pseudoarthrosis. This narrative review examines the current evidence on bone health optimization strategies for spinal deformity patients. Preoperative screening and medical optimization are crucial, with vitamin D supplementation showing particular benefit. Among the pharmacologic agents, bisphosphonates demonstrate efficacy in improving fusion rates and reducing hardware-related complications, though the effects may be delayed. Teriparatide, a parathyroid hormone analog, shows promise in accelerating fusion and enhancing pedicle screw fixation. Newer anabolic agents like abaloparatide and romosozumab require further study but show potential. Romosozumab, in particular, has demonstrated significant improvements in lumbar spine BMD over a shorter duration compared to other treatments. Surgical techniques like cement augmentation and the use of larger interbody cages can mitigate the risks in osteoporotic patients. Overall, a multifaceted approach incorporating medical optimization, appropriate pharmacologic treatment, and tailored surgical techniques is recommended to improve outcomes in adult spinal deformity patients with compromised bone quality. Future research should focus on optimizing the treatment protocols, assessing the long-term outcomes of newer agents in the spine surgery population, and developing cost-effective strategies to improve access to these promising therapies. [ABSTRACT FROM AUTHOR]

Introduction: Increasing incidence of fragility fractures has spurred development of protocols, largely focused on peri-operative care, with numerous proven benefits. The purpose of this investigation was to evaluate outcomes of our hip fracture treatment program regarding successful protocol implementation, compliance, effect on subsequent fracture rates, and mortality during the first decade of adoption. Methods: A retrospective review identified patients >65 years old with fragility hip fractures between 2010 and 2022. The HiROC (+) cohort consisted of patients who received a "High-Risk Osteoporosis Clinic" (HiROC) referral for bone health evaluation and bisphosphonate initiation as indicated. Additional fracture rates and mortality at 3 years were calculated. Protocol implementation and compliance over the first 10 years was analyzed in the four identified cohorts. Results: A total of 1671 fragility hip fractures were identified, with 386 excluded due to insufficient follow-up, with an average age of 81.6 years and a median follow-up of 36.4 months. Of the 1280 included cases, 56% (n = 717) had a HiROC referral placed. HiROC(+) groups had lower subsequent fracture rates at two years, compared to those without referral (28% vs 13%, P < 0.0001) and those completing more steps of the protocol had lower subsequent fracture rates (28% vs 15% vs 13% vs 5%, P < 0.0001). No statistically significant difference was observed between the cohorts for anatomic site of subsequent fractures. Discussion: Greater than half of all eligible patients were successfully captured by the protocol. Patients completing more steps of the protocol had lower subsequent fracture rates. Captured patients demonstrated reduced mortality rates when compared to current literature. Conclusion: Successful implementation of this geriatric hip fracture protocol was associated with reduced additional fractures and mortality rates. Identifying steps of process failures in the protocol can provide opportunities for increased compliance and reduction in future fracture occurrences. [ABSTRACT FROM AUTHOR]

Purpose: This systematic review aimed to determine the effects of maternal exposure to bisphosphonates (BPs) during pregnancy on neonatal outcomes. It aimed to disclosfe the impact of BPs on neonates and identify aspects that require further investigation. Methods: A comprehensive search of PubMed, Science Direct, LILACS, EMBASE, and Web of Science was conducted until August 2022, with no time restrictions. The selection criteria included studies published in English that evaluated pregnant women who were exposed to BPs. Results: From an initial pool of 2169 studies, 13 met the inclusion criteria for this systematic review. These studies collectively included 106 women (108 pregnancies) who were exposed to BPs either before orduring pregnancy. A summary of the key characteristics of the selected studies and the risk of bias assessment are provided. Exposure to BPs occurs at various stages of pregnancy, with different indications for BP treatment. The most frequently reported neonatal outcomes were spontaneous abortion, congenital malformations, hypocalcemia, preterm birth, and low birth weight. Conclusion: Although previous reports have linked BPs before or during pregnancy with adverse neonatal outcomes, these associations should be interpreted with caution. Given the complexity of these findings, further research is necessary to provide more definitive insights to guide clinical decisions regarding the use of BPs in pregnant women. [ABSTRACT FROM AUTHOR]

Osteoporosis is the most common bone disease both worldwide and in the United States, and generally remains subclinical until the occurrence of fracture. With osteoporotic fractures being a substantial source of morbidity and mortality, effective therapies for slowing the decline of bone density in affected individuals are much needed. The standard therapy of osteoporosis may include medication, fall prevention, smoking cessation, avoidance of excess alcohol intake, calcium, and weight-bearing exercise. This article reviews complementary or integrative approaches with evidence for use in osteoporosis. This includes strontium, choline-stabilized orthosilicic acid, isoflavones (including ipriflavone and soy isoflavones), vitamin D, and vitamin K. [ABSTRACT FROM AUTHOR]

Summary: This study uses NHS waiting times and osteoporosis medication community prescription datasets to assess the impact of COVID-19 on DXA waits and osteoporosis medication patterns in England. Results show significant increases in DXA waiting list times and variation in prescription rates. Investment is needed to improve waiting list times. Purpose: This study investigates the impact of COVID-19 on DXA scan waiting lists, service recovery and osteoporosis medication prescriptions in the NHS following the March 2020 national lockdowns and staff redeployment. Methods: Data from March 2019 to June 2023, including NHS digital diagnostics waiting times (DM01) and osteoporosis medication prescriptions from the English Prescribing Dataset (EPD), were analysed. This encompassed total waiting list data across England's seven regions and prescribing patterns for various osteoporosis medications. Analyses included total activity figures and regression analysis to estimate expected activity without COVID-19, using R for all data analysis. Results: In England, DXA waiting lists have grown significantly, with the yearly mean waiting list length increasing from 31,851 in 2019 to 65,757 in 2023. The percentage of patients waiting over 6 weeks for DXA scans rose from 0.9% in 2019 to 40% in 2020, and those waiting over 13 weeks increased from 0.1% in 2019 to 16.7% in 2020. Prescription trends varied, with increases in denosumab, ibandronic acid and risedronate sodium and decreases in alendronic acid, raloxifene hydrochloride and teriparatide. A notable overall prescription decrease occurred in the second quarter of 2020. Conclusion: COVID-19 has significantly increased DXA scan waiting lists with ongoing recovery challenges. There is a noticeable disparity in DXA service access across England. Osteoporosis care, indicated by medication prescriptions, also declined during the pandemic. Addressing these issues requires focused investment and effort to improve DXA scan waiting times and overall access to osteoporosis care in England. [ABSTRACT FROM AUTHOR]

Summary: This study investigates the effects of antiresorptive drugs and risk factors for medication-related osteonecrosis of the jaws in osteoporotic patients undergoing tooth extraction. Among the findings, antiresorptive-treated patients had thicker lamina dura and longer healing times. Additionally, corticosteroid intake and multi-rooted teeth carried a higher osteonecrosis risk. Bone sequestrum indicated osteonecrosis. Purpose: To describe the effects of antiresorptive drugs (ARD) in the maxilla and mandible and risk factors for medication-related osteonecrosis of the jaws (MRONJ) in osteoporotic patients undergoing tooth extractions using clinical data and cone beam computed tomography (CBCT). Methods: This retrospective cohort study collected clinical and CBCT data from 176 patients. The study group (n = 78; 224 extractions) received ARD treatment, underwent tooth extraction, and had a pre-operative CBCT. Additionally, age-, sex-, and tooth-matched controls were selected (n = 98; 227 extractions). Radiographic examinations were performed independently by three calibrated examiners. Statistical analysis included Chi-square, Fisher's exact, Mann–Whitney U, and t-tests to contrast clinical and radiographic data between study and control, MRONJ + and MRONJ − , and bisphosphonate and denosumab patients/sites. Significance was set at p ≤ 0.05. Results: From the study group, 4 patients (5%) and 5 sites (2%) developed MRONJ after tooth extraction. ARD-treated patients exhibited significantly more thickening of the lamina dura and a longer average mucosal healing time (4.4 weeks) than controls (2.6 weeks). In the study group, MRONJ risk significantly increased with corticosteroid intake and in multi-rooted teeth. No significant differences between bisphosphonates and denosumab use were seen in the tomographic features (p > 0.05). Lastly, bone sequestrum was exclusively observed in osteoporotic patients, who exhibited post-operative exposed bone or histological evidence of osteonecrosis. Conclusion: Osteoporotic patients under ARD may exhibit thickening of the lamina dura and prolonged post-operative healing. Among these patients, multi-rooted teeth are at higher risk for MRONJ than single-rooted teeth. Sequester formation is a radiographic indicator of osteonecrosis. [ABSTRACT FROM AUTHOR]

Denosumab and bisphosphonates for primary osteoporosis are generally well-tolerated, but their comparative safety remains unclear. We aimed to explore the comparative safety of denosumab and bisphosphonates in primary osteoporosis. Databases such as PubMed and Google Scholar were searched for relevant peer-reviewed randomized controlled trials published in English (as of December 2023). Trials comparing adverse events (AE) between denosumab and bisphosphonates in patients with primary osteoporosis were investigated. Data were pooled using a fixed- or random-effects model to determine the risk ratios (RR) and 95% confidence intervals (CIs) for various AEs in patients treated with denosumab in comparison to patients treated with bisphosphonates. Eleven trials (5,545 patients; follow-up period: 12–24 months) were included in this meta-analysis. All trials had a risk of bias (e.g., reporting bias linked to secondary endpoints and selection bias linked to random allocation). In comparison to bisphosphonates, denosumab was significantly associated with less withdrawal due to AEs (RR = 0.49; 95% CI 0.34–0.71), more five-point major adverse cardiovascular events (RR = 2.05; 95% CI 1.03–4.09), more cardiovascular AEs (RR = 1.61; 95% CI 1.07–2.41), more infections (RR = 1.14; 95% CI 1.02–1.27), more upper respiratory tract infections (RR = 1.56; 95% CI 1.08–2.25), less vertebral fractures (RR = 0.54; 95% CI 0.31–0.93), and less abdominal pain (RR = 0.44;95% CI 0.22–0.87). We explored the comparative safety of denosumab and bisphosphonates for primary osteoporosis, some of which could be attributed to their beneficial effects. However, all trials had a risk of bias. Further investigations are required to confirm our results. [ABSTRACT FROM AUTHOR]

Summary: Osteoporosis-pseudoglioma syndrome (OPPG) and LRP5 high bone mass (LRP5-HBM) are two rare bone diseases with opposite clinical symptoms caused by loss-of-function and gain-of-function mutations in LRP5. Bisphosphonates are an effective treatment for OPPG patients. LRP5-HBM has a benign course, and age-related bone loss is found in one LRP5-HBM patient. Purpose: Low-density lipoprotein receptor-related protein 5 (LRP5) is involved in the canonical Wnt signaling pathway. The gain-of-function mutation leads to high bone mass (LRP5-HBM), while the loss-of-function mutation leads to osteoporosis-pseudoglioma syndrome (OPPG). In this study, the clinical manifestations, disease-causing mutations, treatment, and follow-up were summarized to improve the understanding of these two diseases. Methods: Two OPPG patients and four LRP5-HBM patients were included in this study. The clinical characteristics, biochemical and radiological examinations, pathogenic mutations, and structural analysis were summarized. Furthermore, several patients were followed up to observe the treatment effect and disease progress. Results: Congenital blindness, persistent bone pain, low bone mineral density (BMD), and multiple brittle fractures were the main clinical manifestations of OPPG. Complex heterozygous mutations were detected in two OPPG patients. The c.1455G > T mutation in exon 7 was first reported. During the follow-up, BMD of two patients was significantly improved after bisphosphonate treatment. On the contrary, typical clinical features of LRP5-HBM included extremely high BMD without fractures, torus palatinus and normal vision. X-ray showed diffuse osteosclerosis. Two heterozygous missense mutations were detected in four patients. In addition, age-related bone loss was found in one LRP5-HBM patient after 12-year of follow-up. Conclusion: This study deepened the understanding of the clinical characteristics, treatment, and follow-up of OPPG and LRP5-HBM; expanded the pathogenic gene spectrum of OPPG; and confirmed that bisphosphonates were effective for OPPG. Additionally, it was found that Ala242Thr mutation could not protect LRP5-HBM patients from age-related bone loss. This phenomenon deserves further study. [ABSTRACT FROM AUTHOR]

Summary: Antiresorptive medications do not negatively affect fracture healing in humans. Teriparatide may decrease time to fracture healing. Romosozumab has not shown a beneficial effect on human fracture healing. Background: Fracture healing is a complex process. Uncertainty exists over the influence of osteoporosis and the medications used to treat it on fracture healing. Methods: Narrative review authored by the members of the Fracture Working Group of the Committee of Scientific Advisors of the International Osteoporosis Foundation (IOF), on behalf of the IOF and the Société Internationale de Chirurgie Orthopédique et de Traumatologie (SICOT). Results: Fracture healing is a multistep process. Most fractures heal through a combination of intramembranous and endochondral ossification. Radiographic imaging is important for evaluating fracture healing and for detecting delayed or non-union. The presence of callus formation, bridging trabeculae, and a decrease in the size of the fracture line over time are indicative of healing. Imaging must be combined with clinical parameters and patient-reported outcomes. Animal data support a negative effect of osteoporosis on fracture healing; however, clinical data do not appear to corroborate with this. Evidence does not support a delay in the initiation of antiresorptive therapy following acute fragility fractures. There is no reason for suspension of osteoporosis medication at the time of fracture if the person is already on treatment. Teriparatide treatment may shorten fracture healing time at certain sites such as distal radius; however, it does not prevent non-union or influence union rate. The positive effect on fracture healing that romosozumab has demonstrated in animals has not been observed in humans. Conclusion: Overall, there appears to be no deleterious effect of osteoporosis medications on fracture healing. The benefit of treating osteoporosis and the urgent necessity to mitigate imminent refracture risk after a fracture should be given prime consideration. It is imperative that new radiological and biological markers of fracture healing be identified. It is also important to synthesize clinical and basic science methodologies to assess fracture healing, so that a convergence of the two frameworks can be achieved. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to investigate the association of bisphosphonates with outcomes related to radiographic changes and pain in hip osteoarthritis (OA) over 4 years. Methods: This study examined data from the Osteoarthritis Initiative (OAI), which included 4088 hips from 2057 participants. Bisphosphonate users were identified as those who reported usage at least three times, including at baseline and during the subsequent 1, 2, 3, and 4‐year follow‐up visits. Non‐users were participants who did not use bisphosphonates in the 5 years preceding the baseline and at subsequent follow‐up visits. Generalized estimating equations were performed to assess the association between bisphosphonate use and outcomes related to radiographic changes and pain in hip OA over a 4‐year follow‐up. Results: The analysis revealed no statistically significant difference between bisphosphonate users and non‐users concerning outcomes related to radiographic changes and pain in hip OA over 4 years. Specifically, the odds ratios for the incidence and transition of radiographic hip OA were 0.55 (95% Confidence Interval [CI]: 0.26 to 1.17) and 0.78 (95% CI: 0.47 to 1.28), respectively. Furthermore, the odds ratios for the development and resolution of frequent hip pain were 1.04 (95% CI: 0.76 to 1.42) and 0.99 (95% CI: 0.72 to 1.36), respectively. Conclusion: The findings from this longitudinal study do not suggest an association between bisphosphonate use and the prevention, slowing, or delay of development and transition of radiographic changes or pain in hip OA over a 4‐year follow‐up. [ABSTRACT FROM AUTHOR]

Introduction: Granulomatosis due to immune reconstitution inflammatory syndrome (IRIS) and disseminated Mycobacterium avium-intracellulare (M. avium) infection may trigger hypercalcemia. Here, we report a rare case of hypercalcemia and acute kidney damage related to IRIS in a person living with Human Immunodeficiency Virus (HIV). Case presentation: A 39-year-old male person living with HIV presented with muscle weakness and unwanted weight loss of 8 kg within the last 2 weeks. Laboratory findings included serum hypercalcemia of 3.27 mmol/mL associated with elevated calcitriol and acute kidney damage. Since the first diagnosis of HIV and concomitant disseminated M. avium infection, the patient received antiretroviral therapy (ART), rifabutin, clarithromycin, and ethambutol. 18Fluoro-D-glucose positron emission computed tomography (18FDG-PET/CT) showed progressive multilocular lymphadenopathy. Biopsy specimen from the duodenum as well as retroperitoneal and mediastinal lymph nodes revealed granulomatous inflammation consistent with IRIS. Treatment with forced diuresis, bisphosphonates, and calcitonin normalized serum calcium and kidney function recovered. Conclusion: Hypercalcemia due to IRIS is a rare differential diagnosis in persons living with HIV and may lead to acute kidney damage, despite sufficient ART and antimycobacterial treatment. [ABSTRACT FROM AUTHOR]

The scientific literature suggests that, if periprosthetic osteolysis (PPO) is not treated, it may have a negative impact on the results of a total hip replacement and possibly result in failure. This systematic review aimed to determine the efficacy of using bisphosphonates preventatively to limit PPO after a total hip arthroplasty (THA). Methods: A systematic review and meta-analysis were conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A PICOS template was developed to ensure a structured approach. A search for relevant studies was performed across four databases, including Pubmed, Scopus, Embase, and Cochrane. They were all last searched on March 1st and were assessed using the Cochrane risk of bias tool for randomised studies. Results: The final analysis included seven studies with a total of 126 study group participants and 144 control group participants. The studies looked at Bony Mass Density in terms of bone loss on Gruen's femoral zones after THA in a bisphosphonate (treatment) and control group (placebo/no treatment). The analysis revealed a statistically significant difference (p < 0.05) in favour of the bisphosphonate group in many of the included studies at 6, 12, and 24 postoperative months. Conclusions: This systematic review and meta-analysis, using the most recent applicable studies, showed the efficacy of bisphosphonates in limiting periprosthetic osteolysis after THA in a period between 6 and 24 postoperative months. Future studies should focus increasing group sizes and collecting results beyond the 2-year mark. [ABSTRACT FROM AUTHOR]

Background: Osteogenesis imperfecta (OI) is an inherited disorder characterized by bone fragility and skeletal alterations. The administration of bisphosphonates (BPs) to patients with OI reduces pain, thereby improving their quality of life. The main mechanism of action of BPs is the inhibition of osteoclast action. In the oral cavity of children with OI during growth and development, physiological processes that require the function of osteoclasts occur. The aim of this investigation was to study the dental development of premolars and the root resorption of primary molars in children with OI medicated with BPs according to age and sex. Methods: An observational and analytical study was designed. The study sample consisted of 26 6- to 12-year-old children with a confirmed diagnosis of OI treated with BPs with available panoramic radiographs. The control group consisted of 395 children with available panoramic radiographs. Both groups were divided into subgroups according to sex and age. The third quadrant was studied, focusing on the first left temporary molar (7.4), the second left temporary molar (7.5), the first left permanent premolar (3.4) and the second left permanent premolar (3.5). The Demirjian method was used to study the dental development of 3.4 and 3.5, and the Haavikko method was used to study the root resorption of 7.4 and 7.5. The Mann‒Whitney U test was used for comparisons, and p < 0.05 indicated statistical significance. Results: The mean chronological age of the 421 patients was 9.21 years (95% CI 9.05–9.37). The sample was reasonably balanced by sex, with 52.5% (221 patients) boys versus 47.5% (200 patients) girls. Delayed exfoliation and tooth development were described in children with OI (p = 0.05). According to sex, the root resorption of primary molars and tooth development were significantly lower in boys in both groups and in girls in the OI group, but the differences between the age groups were not significant. Conclusions: Children with OI treated with BPs exhibit delayed dental development of the premolars and delayed root resorption of the primary molars. Boys exhibited delays in both variables, but the differences by age subgroup were not significant. These clinical findings support the importance of clinically and radiographically monitoring the dental development and root resorption of primary teeth in children with OI treated with BPs to avoid alterations of the eruptive process. [ABSTRACT FROM AUTHOR]

Pregnancy- and lactation-associated osteoporosis (PLO) is a rare type of premenopausal osteoporosis, typically occurring during the third trimester of pregnancy and the early postpartum lactation period. This report presents a case involving severe multiple vertebral fractures due to PLO with low bone mineral density (BMD) and heightened bone turnover. A 39-year-old primiparous Japanese woman reported low back pain (LBP) starting at 28 weeks of pregnancy. The pain temporarily improved after delivery, although the LBP recurred and worsened 2 months into breastfeeding. Thereafter, the patient visited the Obstetrics and Orthopedic departments. Plain radiographs of the thoracic and lumbar spine showed loss of vertebral body height at the T4–12 and L1–3,5 vertebrae, leading to a diagnosis of 13 fractured vertebrae. BMD and serum bone turnover markers revealed low bone density and heightened bone turnover. In the absence of any identified alternative cause of secondary osteoporosis, the diagnosis was severe PLO with 13 vertebral fractures related to pregnancy and lactation. After treatment with bisphosphonates and an active vitamin D analog, the patient exhibited an increased BMD and normalization of bone turnover and resumed regular daily activities. Although the optimal PLO treatment strategy remains uncertain, bisphosphonates are an option; however, bisphosphonates can potentially affect the fetus through placental transfer. Therefore, careful consideration is required for patients planning pregnancy. Despite bisphosphonates' widespread use and cost-effectiveness, selecting PLO medications involves multiple factors, necessitating further research. [ABSTRACT FROM AUTHOR]

Background: Patients with Cushing's disease (CD) often experience slow recovery of bone mineral density (BMD), and the effectiveness of anti-osteoporosis drugs in young CD patients who have achieved biochemical remission after surgery is not well understood. Therefore, we aimed to explore whether bisphosphonates could help accelerate the recovery of osteoporosis in young CD patients with remission. Methods: We retrospectively enrolled 34 young patients with CD who achieved postoperative biochemical remission. All patients suffered from osteoporosis before surgery and were divided into postoperative bisphosphonate treatment group (16 cases) and without bisphosphonate treatment group (18 cases). Clinical data, BMD (Z Value), and bone turnover markers were collected at the time of diagnosis and one year after successful tumor resection. Results: The Z values in the lumbar spine showed slight improvement in both groups at follow-up compared to baseline, but this improvement was not statistically significant. There was no significant difference observed between the two groups at follow-up. One year after operation, bone formation markers (OC and P1NP) were significantly higher than those at baseline in both groups. However, OC and P1NP in the bisphosphonate treatment group were lower than those in control group at one year follow-up. In without bisphosphonate treatment group, β-CTX from follow-up visit was higher than that at baseline, while no significant difference was observed in the bisphosphonate treatment group before and after surgery. Conclusion: Young patients with Cushing's disease combined with osteoporosis might not benefit from bisphosphonate therapy for osteoporosis recovery in the first year after achieving biochemical remission. [ABSTRACT FROM AUTHOR]

Objective: To determine the effect of zoledronic acid (ZA) on the risk of total knee replacement (TKR) in patients with symptomatic knee osteoarthritis and without severe joint space narrowing (JSN). Methods: We included 222 participants (mean age 62 years, 52% female) from the two‐year Zoledronic Acid for Osteoarthritis Knee Pain trial (113 received 5 mg of ZA annually and 109 received placebo) conducted between November 2013 and October 2017. Primary TKR were identified until February 22, 2022. The effect of ZA on TKR risk was evaluated using Cox proportional hazard regression models. Because the treatment effect failed the proportional hazards assumption, a time‐varying coefficients analysis for treatment was conducted by splitting the study into two periods (ie, within and after two years of randomization). Results: Over a mean follow‐up of seven years, 39% and 30% of participants had any TKR in the ZA and placebo groups, and 28% and 18% had TKR in the study knee, respectively. Use of ZA was associated with a higher risk of TKR in any knee (hazard ratio [HR] 4.2, 95% confidence interval [CI] 1.2–14.7) and showed a trend in the study knee (HR 6.8, 95%CI 0.9–53.9) during the trial. In the posttrial period, the risk of TKR was similar in the ZA and the placebo groups for any knee (HR 1.2, 95%CI 0.5–1.8) and the study knee (HR 1.4, 95%CI 0.5–2.2). Conclusion: These results suggest that ZA is not protective against TKR in patients with symptomatic knee osteoarthritis and without severe JSN. [ABSTRACT FROM AUTHOR]

Summary: Osteoporosis treatment following arthroplasty for femoral neck fracture (FNF) is associated with lower rates of periprosthetic fracture (PPF). Our study evaluated the economic viability of treatment in patients following arthroplasty and demonstrates that treatment with oral bisphosphonates can be cost-effective in preventing PPF. Introduction: Osteoporosis treatment following arthroplasty for femoral neck fracture (FNF) is associated with lower rates of periprosthetic fracture (PPF). Although cost-effective in reducing the rate of secondary fragility fracture, the economic viability of osteoporosis treatment in preventing PPF has not been evaluated. Therefore, the purpose of this study is to use a break-even analysis to determine whether and which current osteoporosis medications are cost-effective in preventing PPF following arthroplasty for FNFs. Methods: Three-year average cost of osteoporosis medication (oral bisphosphonates, estrogen hormonal therapy, intravenous (IV) bisphosphonates, denosumab, teriparatide, and abaloparatide), costs of PPF care, and PPF rates in patients who underwent hip arthroplasty for FNFs without osteoporosis treatment were used to perform a break-even analysis. The absolute risk reduction (ARR) related to osteoporosis treatment and sensitivity analyses were used to evaluate the cost-effectiveness of this intervention and break-even PPF rates. Results: Oral bisphosphonate therapy following arthroplasty for hip fractures would be economically justified if it prevents one out of 56 PPFs (ARR, 1.8%). Given the current cost and incidence of PPF, overall treatment can only be economically viable for PPF prophylaxis if the 3-year costs of these agents are less than $1500. Conclusion: The utilization of lower cost osteoporosis medications such as oral bisphosphonates and estrogen hormonal therapy as PPF prophylaxis in this patient population would be economically viable if they reduce the PPF rate by 1.8% and 1.5%, respectively. For IV bisphosphonates and newer agents to be economically viable as PPF prophylaxis in the USA, their costs need to be significantly reduced. [ABSTRACT FROM AUTHOR]

Summary: Post hoc analysis of FRAME and ARCH revealed that on-study nonvertebral and vertebral fractures by Month 12 were less common in women initially treated with romosozumab versus placebo or alendronate. Recurrent fracture risk was also lower in romosozumab‑treated patients, and there were no fracture‑related complications. Results support continuing romosozumab treatment post‑fracture. Purpose: Post hoc analysis evaluating efficacy and safety of romosozumab, administered in the immediate post‑fracture period, in the FRAME and ARCH phase 3 trials. Methods: In FRAME (NCT01575834) and ARCH (NCT01631214), postmenopausal women with osteoporosis were randomized 1:1 to romosozumab 210 mg monthly or comparator (FRAME, placebo; ARCH, alendronate 70 mg weekly) for 12 months, followed by antiresorptive therapy (FRAME, denosumab; ARCH, alendronate). In patients who experienced on-study nonvertebral or new/worsening vertebral fracture by Month 12, we report the following: fracture and treatment‑emergent adverse event (TEAE) incidence through 36 months, bone mineral density changes (BMD), and romosozumab timing. Due to the sample sizes employed, meaningful statistical comparisons between treatments were not possible. Results: Incidence of on-study nonvertebral and vertebral fractures by Month 12 was numerically lower in romosozumab- versus comparator-treated patients (FRAME, 1.6% and 0.5% versus 2.1% and 1.6%; ARCH, 3.4% and 3.3% versus 4.6% and 4.9%, respectively). In those who experienced on-study nonvertebral fracture by Month 12, recurrent nonvertebral and subsequent vertebral fracture incidences were numerically lower in patients initially treated with romosozumab versus comparator (FRAME, 3.6% [2/56] and 1.8% [1/56] versus 9.2% [7/76] and 3.9% [3/76]; ARCH, 10.0% [7/70] and 5.7% [4/70] versus 12.6% [12/95] and 8.4% [8/95], respectively). Among those with on-study vertebral fracture by Month 12, recurrent vertebral and subsequent nonvertebral fracture incidences were numerically lower with romosozumab versus comparator (FRAME, 0.0% [0/17] and 0.0% [0/17] versus 11.9% [7/59] and 8.5% [5/59]; ARCH, 9.0% [6/67] and 7.5% [5/67] versus 15.0% [15/100] and 16.0% [16/100], respectively). In patients with fracture by Month 12, no fracture‑related complications were reported in romosozumab-treated patients. BMD gains were numerically greater with romosozumab than comparators. Conclusion: Data suggest support for the efficacy and safety of continuing romosozumab treatment following fracture. Trial registrations: NCT01575834; NCT01631214. [ABSTRACT FROM AUTHOR]

Introduction: Medication‐related osteonecrosis of the jaw (MRONJ) is uncommon but can result in severe destruction of the jaw. This case–control study investigated the therapeutic effects of daily or weekly administration of teriparatide in the management of MRONJ using a cohort for osteonecrosis of the jaw. Methods: Patients who were diagnosed with MRONJ and consented to teriparatide administration were assigned either to a group of daily injection or of weekly injection and completed a 4‐week course of injection preoperatively and at least an 8‐week course postoperatively. The control group received either the intraoperative rhBMP treatment (CG_BMP) or no additional perioperative treatment (CG_noBMP). The state of MRONJ was evaluated 2 months (T1) and 6 months (T2) postoperatively for all participants. Results: Either group of daily injection (8.35 weeks ± 1.58; n = 17) or weekly injection (9.17 ± 3.79; n = 12) showed significantly faster healing than those of CG_BMP (14.40 ± 6.08; n = 25) or CG_noBMP (15.79 ± 9.79; n = 39). MRONJ was resolved completely in 24 out of 29 participants who completed the course of teriparatide injections, whereas 46.9% of CG showed delayed resolution. Multiple regression analysis indicated 7.50 times (95% CI, 1.77–31.82) more likelihood of complete resolution of MRONJ for participants with teriparatide injections. Conclusion: A course of daily or weekly administration of teriparatide injections may improve treatment outcomes for patients with MRONJ. [ABSTRACT FROM AUTHOR]

BACKGROUND: Vertebral fragility fractures (VFFs) commonly result from low bone mass and microarchitecture deterioration of bone tissue. spinal orthoses are common non-pharmacological options for managing vertebral fracture pain. However, the effects of spinal orthoses on pain, physical functioning, and quality of life (QoL) are still debated. OBJECTIVE: This survey aimed to investigate the patients-reported outcomes of a dynamic spinal orthosis prescribed in the routine clinical practice of VFFs management. METHODS: This multi-center national-wide prospective cohort study assessed older patients (aged > 60 years) diagnosed with acute VFFs and prescribed with a dynamic spinal orthosis (Spinfast®). A survey questionnaire was realized and included sections on patient characterization, osteoporosis characterization, spinal orthosis, clinical outcomes, pain medications, and osteoporosis medications. The questionnaire was administered at baseline and after three months. A total of 68 patients completed the questionnaire at three months. Most patients had one or two VFFs and were treated with pain medications and osteoporosis medications. Compliance and tolerability of the spinal orthosis were assessed, and clinical outcomes such as pain intensity, physical functioning, and QoL were measured. RESULTS: The results showed no significant differences in outcomes between age subgroups. Italian physical medicine and rehabilitation physicians were commonly involved in the management of VFFs patients. Sixty-six patients completed the questionnaire. The results showed that pain intensity, physical functioning and QoL improved after three months of spinal orthosis wearing (p < 0.0001). CONCLUSION: The correct management of VFFs is mandatory to improve pain and reduce disability, and our findings suggested a positive role of dynamic spinal orthosis to improve the comprehensive management of VFFs patients. However, high-quality research trials are warranted to provide clear recommendations for the correct clinical management of VFF. [ABSTRACT FROM AUTHOR]

Objective: To identify radiographic findings suggestive of drug‐induced osteonecrosis and evaluate radiomorphometric patterns indicative of changes in bone mineral density in individuals transplanted for liver disorders using bisphosphonates. Study Design: The study group included panoramic x‐rays of liver transplant patients who are being monitored and who present a clinical status of osteoporosis and use bisphosphonates. The control group was made up of liver transplant patients who did not have osteoporosis. On panoramic radiographs, mental index (MI) and mandibular cortical index (MCI) and the presence of radiographic anomalies suggestive of osteonecrosis were evaluated. Results: There were significant statistical results when comparing the groups in relation to the decrease in bone mineral density (BMD) with MCI‐C3 (p = 0.036), however, there were none in relation to MI (p = 0.14). There were no valid statistical results when relating MCI (p = 0.94) and MI (p = 0.66) with reduced BMD and use of bisphosphonates. Conclusion: Liver transplant individuals using bisphosphonates present greater radiographic signs of bone sclerosis suggestive of a greater propensity to develop osteonecrosis of the jaw and an increased risk of presenting changes suggestive of reduced bone mineral density on panoramic radiographs when compared to liver transplant individuals not using bisphosphonates. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate pre- and post-fracture medical management of osteoporosis among patients who underwent surgical fixation of femoral neck fractures (FNF) and vertebral compression fractures (VCF), and to investigate if there is a difference in treatment, management, and subsequent fractures between FNF and VCF patients. Patients who underwent surgical fixation of FNF or VCF were retrospectively reviewed at a minimum 1 year follow up. Patients were excluded if their fracture was caused by high energy trauma or malignancy, <50 years-old, deceased, or lost to follow up. Patient demographics such as age, sex, BMI, American Society of Anesthesiology Physical Status Classification System and Charleston Comorbidity index were recorded. Management of osteoporosis, including medication regimen and dual-energy X-ray absorptiometry (DEXA) scans were assessed preoperatively and at minimum one year follow up. Subsequent fractures were also recorded. In the analysis of 370 patients (74.7% FNF, 25.2% VCF), demographics showed a predominantly female population (mean age 78.1). Preoperatively, 21.6% were diagnosed with osteoporosis, consistent between FNF and VCF. Postoperatively, there were no significant differences in new osteoporosis diagnoses, bisphosphonate use, or subsequent fractures. VCF patients, however, were more likely to receive denosumab and post-operative DEXA scans (p < 0.05). Within a year, 6.2% experienced subsequent fractures, with no significant FNF-VCF difference. Only 12.7% received appropriate post-operative osteoporosis treatment, 27.1% had DEXA scans, and 25% had a recorded osteoporosis diagnosis. Multivariable analysis highlighted pre-fracture osteoporosis diagnosis as the sole predictor for post-operative DEXA scans and anti-osteoporotic medication (p < 0.001). This study suggests that factors beyond the type of fragility fracture may influence subsequent fracture risk and anti-osteoporotic medication administration in elderly patients. These findings underscore the importance of a comprehensive approach to fracture risk assessment and treatment decisions in this population. III. [ABSTRACT FROM AUTHOR]

Previous studies assessed the effect of extracorporeal shockwave therapy (ESWT) for knee osteoarthritis (OA) among different situations. Thus, results from a meta-analysis regarding this topic may not be reliable due to heterogeneity. A systematic review was conducted on three internet databases, namely Cochrane Library, PubMed, and Embase, gathering pertinent papers from their establishment to March 2024. The search phrases were as follows: "shockwave" OR "shock wave" OR "extracorporeal shockwave" OR "Extracorporeal Shockwave Therapy [MeSH Term]" AND "knee" AND ("osteoarthritis" OR "arthritis" OR "arthritic" OR "osteoarthritis [MeSH term]"). Twenty-four articles (n = 888) were included, with the resulting conclusions demonstrating that ESWT was effective for knee OA compared with sham ESWT; however, ESWT was not effective for patients with severe knee OA. Patients receiving higher energy or higher shock number had significant improvement than those receiving lower energy or less shock number, respectively. Adding ESWT in isokinetic muscular strengthening exercises (IMSE) was more effective than IMSE alone. The efficacy of ESWT was better than other therapies, including intravenously applied prostacyclin and bisphosphonate, corticosteroid injection, kinesiotherapy, hyaluronic acid injection, platelet-rich plasma injection, and physiotherapy. This review demonstrated that ESWT was effective for knee OA. Higher energy and more shock numbers could obtain better efficacy. ESWT could be used as a replacement for some other therapies. [ABSTRACT FROM AUTHOR]

Background: International osteoporosis guidelines have recommended treatment approaches based on fracture risk stratification, in particular, anabolic therapy for patients with very high risk (VHR) of fragility fracture. Aim: To summarise Australian clinicians' perceptions of patients at VHR of fracture. Methods: Australian clinicians invited to educational webinars on anabolic treatments for osteoporosis were surveyed in March and April 2021 about a typical patient they had most recently seen and identified as at VHR of fracture. Results: Of the 268 clinician attendees who were invited to complete the post‐webinar surveys, 67 (25%) responded and permitted the publication of aggregated data. A typical patient perceived to have a VHR of fracture was a woman in her 80's, living at home, who had been diagnosed with osteoporosis between 5 and 10 years ago, and received treatment for 1–5 years' duration, most commonly denosumab. The patient frequently had a T‐score below −3.0 SD (standard deviation), multiple fragility fractures and most commonly suffered a vertebral fracture in the past 12 months, whereas on an adequate regimen of osteoporosis medication. There was a mismatch between the patient being eligible for anabolic therapy (64.2%) and actually having been prescribed an anabolic treatment in the past (20.9%). Conclusions: Australian clinicians' perceptions of patients with a VHR of fracture and the use of anabolic agents appear to be heavily influenced by local reimbursement criteria. The mismatch between patients deemed eligible for reimbursed anabolic therapy and those prescribed an anabolic agent suggests treatment inertia. [ABSTRACT FROM AUTHOR]

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A systematic review was designed to investigate the effect of treatment with oral bisphosphonate (BP) on osseointegration of dental implants and the incidence of BP-related osteonecrosis of the jaw (BRONJ) in postmenopausal women. Multiple electronic databases, including MEDLINE (PubMed), EMBASE, and SCOPUS, were searched to find all eligible articles published since 1990. All titles and abstracts retrieved by searching information sources were evaluated independently by 2 authors against the eligibility criteria. The number of cases ranged from 11 to 235, and the number of controls ranged from 14 to 343. Alendronate was used in all other studies. Risedronate was used in 6 studies, while ibandronate was used in 4 studies. The number of implants in cases ranged from 25 to 1267, while in controls, the number of implants ranged from 28 to 1450. The time between the placement of implant and the follow-up visit ranged from 4–6 months to 8 years. The results show that out of 2582 placed implants, 50 (1.94%) failed in BP-treated patients. This is while out of 4050 placed implants, 188 (4.6%) failed in the non-BP group. The results from the meta-analysis demonstrated that BP therapy is significantly associated with increased implant failure rates (RR = 1.73 [95% CI, 1.03–2.83], P =.04). Overall, the qualitative assessment of this review suggests that oral treatment with BPs in postmenopausal women does not increase the rate of dental implant failure. Thus, further studies with larger sample sizes should compare BP and non-BP groups in regard to dental implants. [ABSTRACT FROM AUTHOR]

Background efficacy of therapeutic cholecalciferol supplementation for severe COVID-19 is sparingly studied. Objective effect of single high-dose cholecalciferol supplementation on sequential organ failure assessment (SOFA) score in moderate-to-severe COVID-19. Methods participants with moderate to severe COVID-19 with PaO2/FiO2 ratio < 200 were randomized to 0.6 million IU cholecalciferol oral (intervention) or placebo. Outcomes primary outcome was change in Day 7 SOFA score and pre-specified secondary outcomes were SOFA and 28-day all-cause mortality. Results in all, 90 patients (45 each group) were included for intention-to-treat analysis. 25(OH)D3 levels were 12 (10–16) and 13 (12–18) ng/ml (P  = 0.06) at baseline; and 60 (55–65) ng/ml and 4 (1–7) ng/ml by Day 7 in vitamin D and placebo groups, respectively. The SOFA score on Day 7 was better in the vitamin D group [3 (95% CI, 2–5) versus 5 (95% CI, 3–7), P  = 0.01, intergroup difference − 2 (95% CI, −4 to −0.01); r  = 0.4]. A lower all-cause 28-day mortality [24% compared to 44% (P  = 0.046)] was observed with vitamin D. Conclusions single high-dose oral cholecalciferol supplementation on ICU admission can improve SOFA score at Day 7 and reduce in-hospital mortality in vitamin D-deficient COVID-19. ClinicalTrials.gov   id: NCT04952857 registered dated 7 July 2021. What is already known on this topic —vitamin D has immunomodulatory role. Observational and isolated intervention studies show some benefit in COVID-19. Targeted therapeutic vitamin D supplementation improve outcomes in severe COVID-19 is not studied in RCTs. What this study adds —high-dose vitamin D supplementation (0.6 Million IU) to increase 25(OH)D > 50 ng/ml is safe and reduces sequential organ failure assessment score, in-hospital mortality in moderate to severe COVID-19. How this study might affect research, practice or policy— vitamin D supplementation in vitamin D-deficient patients with severe COVID-19 is useful may be practiced. [ABSTRACT FROM AUTHOR]

Data on long-term treatment regimens for preventing bone mineral density (BMD) loss that occurs after denosumab (Dmab) withdrawal are scarce. Our aim was to evaluate the long-term changes (12–36 months) in BMD and bone turnover markers in a group of postmenopausal women who had been treated with Dmab and received subsequent treatment with bisphosphonates. Secondary objectives were to evaluate factors associated with BMD loss, to compare the BMD change in patients who received oral vs intravenous bisphosphonates, and to assess the frequency of fragility fractures after Dmab discontinuation. The clinical data of 54 patients, 26 of whom had clinical and DXA assessments at 36 months, were analyzed. After 12 months, the mean LS BMD had decreased by 2.8% (±5.0), FN BMD by 1.9% (±5.8), and TH BMD by 1.9% (±3.7). After 36 months, LS BMD had decreased by 3.7% (±6.7), FN BMD by 2.5% (±7.1), and TH BMD by 3.6% (±5.2). C-terminal cross-linked telopeptide of type I collagen significantly increased during the first 12 months after Dmab withdrawal but then decreased at 36 months. BMD loss at 12 months was higher in patients with more than 30 months of Dmab treatment, but this difference was only statistically significant at FN (−3.3% vs −0.3%, P  = .252 at LS, −3.3% vs 0.3%, P  = .033 at FN, and −2.1% vs 0.9, P  = .091 at TH). There were no statistically significant differences regarding the change in BMD at 12 and 36 months between oral and intravenous treatment. Seven patients suffered incidental vertebral fractures (clinical vertebral fractures: n  = 6, morphometric fractures: n  = 1) three of which were multiple. None of these patients were treated following international or institutional guidelines or recommendations. In summary, our study suggests that bisphosphonates can help maintain BMD for 36 months after Dmab discontinuation. [ABSTRACT FROM AUTHOR]

Chronic diffuse sclerosing osteomyelitis is a very rare condition, described as a non-suppurative, inflammatory disease of the bone and characterized by a proliferative endosteal reaction, which clinically reveals itself with cyclic pain of the jaw and swelling. We reported two clinical cases, where patients suffered recurrent swelling and pain at the mandible irradiating to the preauricular area, denying any previous trauma or significant medical history. Odontogenic causes were excluded. An initial treatment with antibiotics and NSAIDs temporarily relieved the symptoms without complete resolution, prompting further investigations. After a comprehensive array of diagnostic tools (X-rays, CT scans, scintigraphy, bone biopsy, serum markers), both patients were diagnosed with chronic diffuse sclerosing osteomyelitis of the mandible. Bisphosphonates (clodronate and zolendronate) with different treatment schemes were used to treat the condition, until a full recovery from symptoms was reported. Bisphosphonates could therefore represent an effective option in managing this rare but impactful condition. Further research is warranted to better understand the underlying mechanisms of the disease and to optimize treatment strategies. [ABSTRACT FROM AUTHOR]

Purpose: To analyze the association between scoliosis and vertebral refracture after percutaneous kyphoplasty (PKP) in patients with osteoporotic vertebral compression fractures (OVCFs). Methods: A retrospective study was conducted on 269 patients meeting the criteria from January 2014 to October 2022. All patients underwent PKP with complete data and were followed-up for > 12 months. First, it was verified that scoliosis was a risk factor in 269 patients. Second, patients with scoliosis were grouped based on the Cobb angle to evaluate the impact of the post-operative angle. The cox proportional hazards regression analysis and survival analysis were used to calculate the hazard ratio and recurrence time. Results: A total of 56 patients had scoliosis, 18 of whom experienced refractures after PKP. The risk factors for vertebral refractures included a T-score < − 3.0 and presence of scoliosis (both p < 0.001). The results indicated that the vertebral fractured arc (T10 − L4) was highly influential in scoliosis and vertebral fractures. When scoliotic and initially fractured vertebrae were situated within T10 − L4, the risk factors for vertebral refracture included a postoperative Cobb angle of ≥ 20° (p = 0.002) and an increased angle (p = 0.001). The mean recurrence times were 17.2 (10.7 − 23.7) months and 17.6 (7.9 − 27.3) months, respectively. Conclusion: Osteoporosis combined with scoliosis significantly increases the risk of vertebral refractures after PKP in patients with OVCFs. A postoperative Cobb angle of ≥ 20° and an increased angle are significant risk factors for vertebral refractures when scoliotic and initially fractured vertebrae are situated within T10 − L4. [ABSTRACT FROM AUTHOR]

Objectives: To verify medication-related osteonecrosis of the jaw (MRONJ) frequency among patients with plasma cell myeloma (PCM) that had been treated with bisphosphonates, to identify predisposing factors that could influence the development of osteonecrosis. Methods: This observational retrospective study was performed at the Department of Hematology of Hospital Center of Porto (CHUP), Portugal. Results: The study population (n = 112) had a 15.2% (n = 17) prevalence of osteonecrosis. Clinically, bone exposure was the most frequently observed sign, present in 100% (n = 17) of the patients, followed by inflammation in 82.4% (n = 14), orofacial pain in 70.6% (n = 12), suppuration in 47.1% (n = 8), and intra or extra-oral fistula in 17.6% (n = 3) of the cases. The most frequent triggering local factor was dental extraction (82.4%). There was a dependence between the presence of extractions and the development of MRONJ (p < 0.001) but not with the time elapsed from the initiation of infusions with BPs and dental extractions (p = 0.499). In the sample of patients with multiple myeloma (MM), 13.8% were found to be more likely to develop MRONJ after an extraction. Conclusions: The most common local predisposing factor was dental extraction. No dependence was observed between the development of osteonecrosis and the time elapsed from the beginning of treatment with bisphosphonates infusions to surgical procedures. [ABSTRACT FROM AUTHOR]

Bisphosphonates have been associated with a decreased risk of revision surgery after total joint arthroplasty of the hip or knee (TJA) because of their effects on decreased periprosthetic bone loss and prosthetic migration. However, the results in the early literature are inconsistent, and the influence of bisphosphonates on associated complications and subsequent TJA remains unknown. This study investigated the association between the use of bisphosphonates and the risk of adverse outcomes after primary TJA. This matched cohort study utilized the National Health Insurance Research Database in Taiwan to identify patients who underwent primary TJA over a 15-year period (January 2000–December 2015 inclusive). Study participants were further categorized into two groups, bisphosphonate users and nonusers, using propensity score matching. The Kaplan–Meier curve analysis and adjusted hazard ratios (aHRs) of revision surgery, adverse outcomes of primary surgery and subsequent TJA were calculated using Cox regression analysis. This study analyzed data from 6485 patients who underwent total hip arthroplasty (THA) and 20,920 patients who underwent total knee arthroplasty (TKA). The risk of revision hip and knee arthroplasty was significantly lower in the bisphosphonate users than in the nonusers (aHR, 0.54 and 0.53, respectively). Furthermore, the risk of a subsequent total joint arthroplasty, adverse events and all-cause mortality were also significantly reduced in the bisphosphonate users. This study, involving a large cohort of patients who underwent primary arthroplasties, revealed that bisphosphonate treatment may potentially reduce the risk of revision surgery and associated adverse outcomes. Furthermore, the use of bisphosphonates after TJA is also associated with a reduced need for subsequent arthroplasty. Research Registration Unique Identifying Number (UIN): ClinicalTrials.gov Identifier—NCT05623540 (https://clinicaltrials.gov/show/NCT05623540). [ABSTRACT FROM AUTHOR]

Summary: Bone strength estimates are important for fracture prevention. This study compared bone strength changes in postmenopausal women with low bone mass who were assigned to 12 months of exercise, a bone medication, or control. Exercise and bone medications benefited structure at the hip. Structure should be considered in fracture prevention research. Purpose: Exercise and bisphosphonates reduce fracture risk, but their impact on estimates of bone strength remains uncertain. This study compared changes in tibial bone strength using peripheral quantitative computed tomography (pQCT) and hip structure analysis (HSA) outcomes from dual-energy X-ray absorptiometry (DXA) scans in postmenopausal women with low bone mass assigned to 12 months of exercise, risedronate, or control. Methods: In this RCT, 276 postmenopausal women within 6 years of menopause were randomly assigned to three groups: exercise (92), risedronate (91), or control (93). Exercise included weighted jogging and progressive resistance exercises; risedronate treatment was 150 mg monthly; all groups received calcium and vitamin D. pQCT and DXA images were obtained at baseline and 6 and 12 months and compared between groups over time. Results: Participants had a mean (± SD) age of 54.5 (± 3.2) years with an average of 36.7 (± 40.7) months postmenopause. No significant differences were found between groups for the change in pQCT outcomes (volumetric bone mineral density, area, and strength estimates). At 12 months, mean percent differences (95% CI) in HSA measures between exercise and controls were as follows: intertrochanteric, cross-sectional area 2.25% (0.28, 4.12) (p =.03), cross-sectional moment of inertia (CSMI) 5.67% (1.47, 9.87) (p <.01), and section modulus (SM) 4.38% (1.02, 7.74) (p =.01), and narrow neck, average cortical thickness 2.37% (−0.08, 4.83) (p =.031). Mean percent differences (95% CI) in HSA measures between risedronate and control were as follows: intertrochanteric, CSMI 4.28% (−0.24, 8.81) (p =.03) and SM 3.35% (−0.21, 6.91) (p =.03), and shaft, subperiosteal width 0.82% (0.05, 1.58) (p =.047), CSMI 2.53% (0.88, 4.18) (p =.004), and SM 1.57% (0.34, 2.8) (p =.008). Exercise maintained neck-shaft angle compared to both control 1.27% (0.13, 2.41) (p =.04) and risedronate 1.31% (0.23, 2.39) (p =.03). All other differences for changes in HSA outcomes over time were not significantly different between the exercise and risedronate groups. Conclusion: Exercise and bisphosphonates may influence structural and strength estimates at the hip, but not at peripheral sites (tibia). Neither exercise nor bisphosphonates were found to be superior in improving estimates of hip bone strength. [ABSTRACT FROM AUTHOR]

Objective: Application of an optical method for the identification of antiresorptive drug‐related osteonecrosis of the jaw (ARONJ). Methods: We introduce shifted‐excitation Raman difference spectroscopy followed by U‐Net deep neural network refinement to determine bone tissue viability. The obtained results are validated through established histological methods. Results: Discrimination of osteonecrosis from physiological tissues was evaluated at 119 distinct measurement loci in 40 surgical specimens from 28 patients. Mean Raman spectra were refined from 11,900 raw spectra, and characteristic peaks were assigned to their respective molecular origin. Then, following principal component and linear discriminant analyses, osteonecrotic lesions were distinguished from physiological tissue entities, such as viable bone, with a sensitivity, specificity, and overall accuracy of 100%. Moreover, bone mineral content, quality, maturity, and crystallinity were quantified, revealing an increased mineral‐to‐matrix ratio and decreased carbonate‐to‐phosphate ratio in ARONJ lesions compared to physiological bone. Conclusion: The results demonstrate feasibility with high classification accuracy in this collective. The differentiation was determined by the spectral features of the organic and mineral composition of bone. This merely optical, noninvasive technique is a promising candidate to ameliorate both the diagnosis and treatment of ARONJ in the future. [ABSTRACT FROM AUTHOR]