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Purpose: To evaluate the efficacy of combined therapy of teriparatide and raloxifene on the osseointegration of titanium dental implants in a rabbit model of osteoporotic bone. Materials and Methods: Sixty female rabbits were randomly divided into six groups. The sham ovariectomy group (control) consisted of animals that received no medication. Animals in the ovariectomy group (OVX) underwent ovariectomy and received no medication. The combined group consisted of ovariectomized animals that received combined teriparatide (10 mg/kg) for 12 weeks and raloxifene (10 mg/kg) for 12 weeks. The sequential group (SEQ) consisted of ovariectomized animals that received teriparatide (10 mg/kg) for the first 6 weeks and raloxifene therapy (10 mg/kg) for the following 6 weeks sequentially. The parathormone (PTH) and raloxifene (RAL) groups consisted of ovariectomized animals that received only teriparatide (10 mg/kg) for 12 weeks or raloxifene (10 mg/kg) for 12 weeks, respectively. Dental implants (Bilimplant) were placed in the proximal metaphysis of both tibias in all rabbits. Histomorphometric and microCT studies were performed on the specimens obtained from the right tibia bone. Removal torque (RTQ) and implant stability quotient (ISQ) tests were performed on the specimens obtained from the left tibia bone. The results were compared and evaluated statistically. Results: RTQ analysis revealed a statistically significant difference between the mean values of the combined group (93.01 ± 27.19 Ncm) and the OVX group (49.6 ± 12.5 Ncm) (P = .015). The highest mean T0 (implantation day) value was obtained in the control group (67.1 ± 3.4 Ncm), and the lowest mean value was obtained in the OVX group (61.4 ± 3.8 Ncm). The highest T1 mean (3 months after implantation) was obtained by the combined group (76.6 ± 3.8 Ncm), and the lowest mean was obtained by the OVX group (68.9 ± 6.2 Ncm). Histomorphometric analyses showed that the mean percentage of bone-to-implant contact (BIC%) of the combined group (51.2%) was significantly higher than that of the OVX group (28.6%) (P =.006). In the microCT examinations, it was found that the mean BIC% value of the combined group (41.1%) was significantly higher than that of the OVX group (24.1%) (P < .001). Conclusions: According to the results of the current study, combined therapy of teriparatide and raloxifene improves the BIC and osseointegration of titanium dental implants in osteoporotic bone compared with sequential or independent therapy with these agents. [ABSTRACT FROM AUTHOR]

Osteoporosis is a metabolic bone disorder for which treatment options include antiresorptive therapies (e.g., bisphosphonates, denosumab); anabolics (e.g., teriparatide, abaloparatide); and dual mechanisms (e.g., romosozumab). Management of osteoporosis with concurrent antiresorptive and anabolic agents may be superior to monotherapy, as demonstrated in the DATA trial with the combination of denosumab and teriparatide. However, there is limited experience with the combination of denosumab and romosozumab, which may be an alternative antiresorptive/anabolic regimen for individuals who are not candidates for PTH receptor agonists. In this case, we present a young man with glucocorticoid-induced osteoporosis who could not tolerate a daily injectable anabolic and who experienced improvement in bone mineral density with concurrent denosumab and off-label romosozumab administration. [ABSTRACT FROM AUTHOR]

Purpose: This study evaluates sex differences and predictors of anti-osteoporosis medication (AOM) use following a hip fracture, with a focus on older men who exhibit higher mortality rates post-fracture compared to women over the age of 65. Methods: Participants included 151 men and 161 women aged 65 and older with hip fractures. The outcome, AOM use, was assessed at baseline (≤ 22 days of hospitalization) and at 2, 6, and 12 months post-hip fracture. Generalized estimating equations (GEE) modeled sex differences and predictors of AOM use during the year post-fracture in 255 participants with complete baseline data and ≥ 1 follow-up observation. Results: Of the 312 participants, only 53 used AOM at baseline, and 35 initiated use during follow-up. In the unadjusted GEE model, AOM use was significantly less likely in men (OR = 0.42; 95% CI, 0.22–0.78) compared to women. For both men and women, baseline use of AOM was a significant predictor (OR = 28.3; 95% CI, 5.4–148.0 vs. 41.6; 95% CI, 14.0–123.0). The other significant predictors by sex were osteoporosis diagnosis (OR = 3.19; 95% CI, 1.16–8.77) and minimal alcohol use (OR = 3.26; 95% CI, 1.34–7.94) for women versus age (OR = 1.09; 95% CI, 1.01–1.18) for men. Conclusion: In older adults with hip fractures, AOM use is low over the year post-fracture and men are less likely to report AOM use compared to women which has implications for important sex differences in predictors of use. Further research is needed to address overall disparities and sex differences in AOM use. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the effect of applying a matrix metalloproteinase (MMP) inhibitor on the fracture resistance of root-filled teeth restored with Everstick fiber-reinforced composite resin. Subjects and Methods: After the selection of 60 freshly extracted human mandibular first molar, root canal access and standard uniformly sized mesio-occluso-distal (MOD) cavities were made and the teeth were randomly assigned into three groups (n = 20 each): Group I, the MOD cavity was first lined with flowable composite resin and then restored with composite resin. In Group II, Everstick fiber was placed into the bed of flowable composite in buccal–pulpal–lingual direction before the composite restoration was placed. In Group III, after etching of the cavity, a 2% chlorhexidine MMP inhibitor was applied. Then, the MOD cavity was restored same as group II. A universal testing machine was employed to compressively load the teeth at a cross-head speed of 0.5 mm/min till fracture. The maximum fracture loads were recorded in Newtons (N) and data were analyzed with one-way ANOVA and post-hoc Tukey tests. Results: Group III exhibited significantly higher fracture resistance compared to all other groups (P < 0.001), whereas Group I demonstrated the lowest fracture resistance. Conclusion: The utilization of Everstick glass fiber, combined with MMP inhibitor treatment, yielded the greatest fracture resistance. Hence, this method may be prioritized over conventional restoration techniques for strengthening root canal-treated teeth with structurally compromised crowns. [ABSTRACT FROM AUTHOR]

Introduction: Pregnancy and lactation-associated osteoporosis (PLO) is a rare condition characterized by fragility fractures occurring during late pregnancy or lactation, primarily affecting the spine and causing significant morbidity and back pain. PLO can lead to mobility impairment and work incapacity, with recovery taking up to several years. Due to the lack of clinical trials, treatment strategies remain poorly defined, historically focusing on calcium supplements, vitamin D, and weaning from breastfeeding. However, recent attention has turned to teriparatide (TPD) as an option due to its anabolic properties and potential suitability for women of childbearing age. Methods: This review evaluates TPD's use in PLO treatment, using published systematic reviews and case studies. Over 300 cases with PLO were identified through PubMed, Google Scholar, and Cochrane searches until August 2023. Results: We identified 175 cases with PLO treated with TPD alone or followed by antiresorptive therapy. Most women (85.7%) were primiparas. The mean ± SD duration of TPD use was 15 ± 6 months. Among the study patients, 91.4% used TPD alone, while 8.6% (15/175) utilized sequential therapy. Approximately 93% of our cohort exhibited potential risk factors for PLO. Despite the increased risk of recurrent fractures in PLO, only 14.7% (20/175) of those treated with TPD sustained new fractures during a 9-month to 9 years' follow-up period. The mean ± SD percent increase in BMD at the LS was 21.14% ± 7.4%, and at the FN it was 12.1% ± 9.3%. The baseline Z-scores at the LS ranged from –3.3 (–3.7 to –2.7), while the baseline Z-scores at the FN ranged from −2.0 (−2.7 to −1.5). Conclusion: This review emphasizes PLO severity, advocating for increased awareness and timely interventions. TPD emerges as a promising therapeutic option in certain cases. [ABSTRACT FROM AUTHOR]

Excessive dietary fat intake increases plasma lipid levels and has been associated with reduced bone mineral density (BMD) and increased risk of osteoporotic fracture, especially in older postmenopausal women. The objective of this study was to investigate whether there are sex-related differences in lipid metabolism that could have an impact on large-scale bone regeneration. Because ribs provide a unique exception as the only bones capable of completely regenerating large-scale defects, we used a rib resection mouse model in which human features are recapitulated. After 10 days of exposure to a low-fat diet or high-fat diet (HFD), we performed large-scale rib resection surgeries on male and female mice (6–7 weeks old) with deletion of the low-density lipoprotein (LDL) receptor (Ldlr−/−) and age- and sex-matched wild-type (WT) mice were used as controls. Plasma analysis showed that short-term exposure to HFD significantly increases total cholesterol, LDL cholesterol, and triglycerides levels in Ldlr−/− mice but not in WT, with no differences between males and females. However, under HFD, callus bone volume was significantly reduced exclusively in male Ldlr−/− mice when compared to WT, although these differences were no longer apparent by 21 days after resection. Regardless of diet or genotype, BMD of regenerated ribs did not differ significantly between groups, although male mice typically had lower average BMD values. Together, these results suggest that short-term hyperlipidemia has transient effects on large-scale bone regeneration exclusively in male mice. [ABSTRACT FROM AUTHOR]

Introduction: So far, only 11 PTH mutations have been described as causes of familial isolated hypoparathyroidism (FIH). In this report, we describe a family with FIH but with significant elevation of functionally inactive PTH due to a PTH mutation. We also show a positive therapeutic outcome of recombinant human PTH (teriparatide) therapy in one of the siblings who was not well controlled on large doses of calcitriol and calcium replacement therapy. Case description: The proband is a 34-year-old woman who has a history of chronic severe hypocalcemia (HypoCa) since birth. She and her three brothers (33-year-old male twins, and a 21-year-old male) were diagnosed with pseudohypoparathyroidism type 1b (PHPT 1b) based on the presence of chronic HypoCa (serum Ca 1.6-1.85 mmol/l) since birth associated with significantly elevated plasma PTH levels in the range of 310-564 pg/dl (normal range 10-65) and absence of signs of Albright hereditary osteodystrophy. Molecular studies: WES showed no pathogenic, likely pathogenic or variants of unknown significance in any known calcium-associated genetic disorder but a bi-allelic variant in the PTH itself ((NM_000315.4:c.128G>A, p.Gly43Glu). This was confirmed by Sanger sequencing in the patient and her affected brothers. Management: Because the patient's HypoCa was not controlled on large doses of calcitriol and calcium carbonate, a trial of teriparatide 20 mcg SC daily was started and resulted in normalization of calcium, decline in PTH levels and significant improvement in her general wellbeing. Conclusion: High PTH in the presence of congenital hypocalcemia is not always due to receptor or post-receptor defect and can be due to a biologically inactive mutated PTH. In such cases, treatment with teriparatide may result in stabilization of biochemical profile and improvement in quality of life. [ABSTRACT FROM AUTHOR]

Background: Periprosthetic bone loss is a well‐known phenomenon following total hip arthroplasty (THA). However, the choice of drugs for prevention remains controversial. Therefore, the aim of this study was to determine the best drug to treat periprosthetic bone loss by comparing changes in bone mineral density (BMD) at different times after THA. Methods: A comprehensive search of five databases and two clinical trial registration platforms was undertaken from their inception through to August 31, 2023 to identify eligible randomized controlled trials. A Bayesian network meta‐analysis (NMA) was carried out for calculating the standardized mean difference (SMD) and the surface under cumulative ranking curve (SUCRA) of the BMD in calcar (Gruen zone 7) at 6 months, 12 months, and 24 months and over. Results: Twenty‐nine trials involving 1427 patients and 10 different interventions were included. The results demonstrated that at 6 months, denosumab had the highest ranking (SUCRA = 0.90), followed by alendronate (SUCRA = 0.76), and zoledronate (SUCRA = 0.73). At 12 months, clodronate ranked highest (SUCRA = 0.96), followed by denosumab (SUCRA = 0.84) and teriparatide (SUCRA = 0.82). For interventions with a duration of 24 months and over, denosumab had the highest SUCRA value (SUCRA = 0.96), followed by raloxifene (SUCRA = 0.90) and zoledronate (SUCRA = 0.75). Conclusion: Investigating the existing body of evidence revealed that denosumab demonstrates potential as an intervention of superior efficacy at the three specifically examined time points. However, it remains crucial to conduct further research to confirm these findings and determine the most effective treatment strategy. [ABSTRACT FROM AUTHOR]

A single‐center, randomized, open, 2‐period, self‐crossover, single‐dose trial was conducted to evaluate the bioequivalence of the test (T) and reference (R) preparations in healthy adult female subjects under fasting conditions. Seventy‐six subjects were enrolled in the study, and subjects were randomly divided into 2 groups at a 1:1 ratio and were administered once per period, with a 4‐day washout period. In each period, plasma drug concentrations, blood calcium changes, and antibodies were determined for pharmacokinetics, pharmacodynamics, and immunogenicity analysis, respectively, and adverse events were recorded for safety analysis. The 90% confidence intervals for the geometric mean ratios (T:R) of maximum plasma concentration, area under the plasma concentration‐time curve from time 0 to the last measurable concentration, and area under the plasma concentration‐time curve from time 0 to infinity were within the predefined bioequivalence criterion of 80%‐125%, indicating bioequivalence between the T and R preparations under fasting conditions. Comparable serum calcium levels demonstrated pharmacodynamics similarity, and no differences were found in immunogenicity profiles. Additionally, the incidence of adverse reactions to the T preparation was 18.4% lower than that of the R preparation (31.6%). This study confirmed the bioequivalence of the T and R preparations under fasting conditions, along with comparable immunogenicity profiles and good safety. [ABSTRACT FROM AUTHOR]

Objectives: The present study aimed to assess the effects of blackcurrant (BC) anthocyanins on concentrations of microbial-derived short-chain carboxylic acids (SCCAs) and metabolites of phytoestrogens. We then examined their associations with six-month changes in whole-body bone mineral density (BMD) and biomarkers of bone metabolism. Methods: Fecal and blood samples from a pilot randomized controlled trial were collected and analyzed from 37 eligible peri- and early postmenopausal women aged 45–60 years who were randomized into one of three treatment groups consuming one placebo capsule (control), 392 mg BC (low BC) or 784 mg BC (high BC) daily for six months. Results: Significant differences were observed between groups at baseline in acetic, propionic, valeric, caproic and heptanoic acids (p < 0.05). Isobutyric acid significantly decreased from baseline (0 months) to six months in the control group (p < 0.05) and the high BC group had a significantly greater concentration than the control group at six months (p < 0.05). Butyric acid was significantly greater in the high BC group than low BC at six months (p < 0.05). Six-month changes in caproic and isobutyric acids showed weak correlations with changes in whole-body BMD (r = 0.3519, p < 0.05 and r = 0.3465, p < 0.05, respectively). Isovaleric and valeric acids displayed weak correlations with BALP (r = 0.3361, p < 0.05) and OPG (r = 0.3593, p < 0.05), respectively. Enterodiol was positively correlated with BALP (r = 0.6056, p < 0.01) while enterolactone was positively correlated with osteocalcin (r = 0.5902, p < 0.001) and negatively correlated with sclerostin (r = −0.3485, p < 0.05). Conclusions: The results suggest that BC may be a potential dietary agent to reduce postmenopausal bone loss through modulating microbially-derived SCCAs and phytoestrogen metabolites. [ABSTRACT FROM AUTHOR]

X‐linked hypophosphatemia (XLH) is a rare genetic disorder caused by excessive fibroblast growth factor 23 (FGF23), leading to low serum phosphate levels resulting in increased risk of fractures and pseudofractures. Burosumab is indicated for the treatment of XLH. In this work, we aimed to understand the quantitative relationship between burosumab‐treatment‐induced improvements in serum phosphate and reduction in fracture and pseudofracture counts in adults with XLH. Burosumab pharmacokinetic pharmacodynamic data from nine clinical studies were first utilized to update a prior population pharmacokinetic pharmacodynamic (PPKPD) model. The updated PPKPD model predictions for serum phosphate exposures along with other factors (i.e., time and treatment) were utilized to evaluate the relationship on fracture counts using Poisson model. The updated PPKPD model suggested that burosumab concentrations required for 50% of maximal effect decreased with increasing baseline serum phosphate levels. A Poisson model with time from baseline, average serum phosphate, and burosumab treatment described the time‐varying fracture and pseudofracture count data appropriately. The model suggested a baseline rate of fracture and pseudofracture of 1.87 counts. The model predicted that fracture counts decrease by 1% each week, and by 23% with each unit increase (1.0 mg/dL) in average serum phosphate from lower limit of normal (2.5 mg/dL). An additional 1% decrease in fracture count each week was attributed to burosumab treatment that could not be explained by improvements in serum phosphate. Overall, the model quantified the relationship between burosumab‐treatment‐induced serum phosphate improvements and reduction in fracture and pseudofracture counts in patients with XLH over time. [ABSTRACT FROM AUTHOR]

Background: Both lipid metabolism and obesity are crucial factors in osteoporosis, influencing the relevance of the cardiometabolic index (CMI), a new body fat index incorporating obesity and lipid metrics. Our study aims to explore the relationship between CMI and lumbar spine bone mineral density (BMD) and the mediating role of body fat percentage. Methods: Utilizing the National Health and Nutrition Examination Survey (NHANES) data from 2011 to 2018, we conducted a cross-sectional analysis. We employed multiple linear regression models, subgroup analyses, generalized additive models (GAM), smooth curve fitting, and mediation analysis to evaluate the linear and nonlinear relationships between CMI and lumbar spine BMD. Results: The study involved 5,124 participants with an average lumbar spine BMD of 1.03 ± 0.15 g/cm2. We identified a negative correlation between CMI and lumbar spine BMD (β = -0.015; 95% CI: -0.023, -0.008). Nonlinear associations were evident, with inflection points at CMI values of 1.12 and 2.86. Subgroup analyses showed consistent negative correlations across all categories without significant differences (p for interaction > 0.05). Moreover, body fat percentage negatively correlated with BMD (β = -0.005; 95% CI: -0.006, -0.004) and mediated 9.41% of the relationship between CMI and BMD. Conclusion: Increased CMI levels are associated with lower lumbar spine BMD, with body fat percentage significantly mediating this relationship. This underscores the importance of managing body composition in the context of bone health, highlighting CMI's potential utility in osteoporosis risk assessment. [ABSTRACT FROM AUTHOR]

Summary: The study found that in osteoporosis patients who had not previously received bisphosphonate treatment and were in a treatment cycle of over 12 months, both teriparatide and denosumab significantly increased bone mineral density compared to bisphosphonates. Additionally, teriparatide was also shown to significantly decrease the risk of fractures. Objective: The systematic review and meta-analysis aimed to assess and compare the safety and efficacy of teriparatide vs. bisphosphonates and denosumab vs. bisphosphonates in patients with osteoporosis who had not previously received bisphosphonates. Methods: We conducted a search of published literature from inception to May 31, 2023, including databases such as PubMed, Embase, Cochrane Library, CNKI, SinoMed, VIP, and WanFang. The study only included head-to-head randomized controlled trials (RCTs) that compared teriparatide and denosumab with bisphosphonates to treat patients with osteoporosis. Fixed-effect model and random-effect model were used due to clinical heterogeneity. Meta-analysis was performed via Stata 17.0. Results: A total of 6680 patients were enrolled across 23 eligible trials. The results of the meta-analysis showed that teriparatide was superior to bisphosphonates in decreasing the risk of fracture (risk ratio (RR) = 0.61, 95% confidence interval (CI) (0.51, 0.74), P < 0.001). Denosumab showed no benefit compared to bisphosphonates in reducing the risk of fracture in treating osteoporosis (RR 0.99, 95% CI (0.62, 1.57), P = 0.96). Compared with bisphosphonates, teriparatide and denosumab could significantly improve femoral neck, total hip, and lumbar spine bone mineral density (BMD) (P < 0.05). Furthermore, teriparatide and denosumab did not increase the incidence of adverse events (teriparatide vs. bisphosphonates, RR 0.92, 95% CI (0.79, 1.08), P = 0.32; denosumab vs. bisphosphonates, RR 0.98, 95% CI (0.95, 1.02), P = 0.37). Conclusions: Teriparatide is superior to bisphosphonates in decreasing the risk of fracture in patients with osteoporosis. In addition, teriparatide and denosumab were more efficacious than bisphosphonates in increasing the percentage change in BMD at the femoral neck, total hip, and lumbar spine. [ABSTRACT FROM AUTHOR]

Objective: To compare the efficacy and safety of denosumab and teriparatide versus oral bisphosphonates to treat postmenopausal osteoporosis. Summary of Background Data: While bisphosphonates have historically been the cornerstone of pharmacological management for bone protection in patients, emerging evidence suggests that teriparatide and denosumab warrant further investigation as potential first-line treatments. The optimal choice among denosumab, teriparatide, and oral bisphosphonates for the treatment of postmenopausal osteoporosis remains a subject of ongoing debate and controversy within the scientific community. Methods: This systematic review adhered meticulously to the rigorous standards outlined by the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines as well as the Cochrane Collaboration recommendations. Additionally, it employed the AMSTAR (Assessing the methodological quality of systematic reviews) criteria to ensure methodological robustness and enhance the credibility of the findings. A systematic electronic search was conducted across Web of Science, PubMed, and the Cochrane Library databases from their inception dates up to February 2024. Results: In this meta-analysis of studies, our findings suggest that compared to bisphosphonates, both teriparatide and denosumab demonstrated notable increases in percentage changes in lumbar spine bone mineral density (BMD) among postmenopausal osteoporosis patients. Furthermore, denosumab exhibited superiority over teriparatide and oral bisphosphonates in enhancing percentage changes in both femoral neck and total hip BMD, indicating its potential as a more efficacious option. Regarding safety outcomes, no significant differences were observed in the incidence of serious adverse events among patients treated with teriparatide, denosumab, and bisphosphonates. However, teriparatide showed superiority over oral bisphosphonates in terms of a lower risk of general adverse events, suggesting a favorable safety profile. Conclusion: In conclusion, our study suggests that teriparatide and denosumab demonstrate comparable or potentially superior efficacy and safety profiles compared to oral bisphosphonates for the treatment of postmenopausal osteoporosis. [ABSTRACT FROM AUTHOR]

Aims Methods Results Conclusions Biosimilar products have clinical characteristics similar to those of brand‐name products and can reduce medical costs. However, the use of biosimilar products for osteoporosis treatments remains limited due to concerns regarding its safety and efficacy. We aimed to clarify the effectiveness and safety of the biosimilar teriparatide compared with those of the reference product using the incidence of new fractures and osteosarcoma as outcomes in osteoporosis patients.This study used the DeSC database, which contains medical claims data for various insurers in Japan. We included patients with osteoporosis aged ≥65 years who newly received either biosimilar teriparatide or the reference products between April 2019 and November 2022. Competing risk analyses were performed with adjustments for patient characteristics. The primary and secondary outcomes were the occurrence of new fractures and osteosarcoma, respectively.Among 45 861 included patients, 3613 and 42 248 were in the biosimilar and reference product groups, respectively. The median follow‐up duration was 439 days. New fractures occurred in 6.7% of patients. Cumulative incidence function curves showed similar risks of new fractures over time in both groups. The cause‐specific hazard ratio for new fractures was 0.95 (95% confidence interval: 0.82–1.11) for the biosimilar group compared with that of the reference product group. The incidence of osteosarcoma did not differ significantly between the groups (P = .559).The biosimilar teriparatide showed effectiveness and safety comparable with those of the reference products in treating osteoporosis patients. Our results suggest that clinicians need not hesitate to prescribe biosimilar teriparatide for osteoporosis patients. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to compare treatment satisfaction with two dosing regimens (two teriparatide [TPTD] self-injection systems) in osteoporosis patients at high risk of fracture. Materials and methods: In this open-label crossover randomized trial comparing self-injected once-daily (1/D)-TPTD with self-injected twice-weekly (2/W)-TPTD, three satisfaction variables were evaluated by questionnaire for 2 years. The primary endpoint was overall satisfaction and secondary endpoints were satisfaction with treatment effectiveness and with utility of the self-injection device. Changes in quality of life (QOL) assessed by EuroQol-5 Dimension, pain assessed by visual analogue scale (VAS), and anthropometric parameters were also analyzed. Safety was evaluated based on the incidence and severity of adverse events (AEs). Results: The 1/D-TPTD and 2/W-TPTD groups consisted of 180 (75.9 ± 7.3 years) and 179 (age: 75.5 ± 6.9 years) patients, respectively. After 26 weeks of treatment, no significant between-group difference in the persistence rate (79.4% vs 72.6% in the 1/D-TPTD and 2/W-TPTD groups, respectively), distributions of overall satisfaction scores, and satisfaction with treatment (p > 0.05) were observed. However, several items of satisfaction with the utility of the injection device were significantly higher in the 2/W-TPTD group (p < 0.05). Statistical improvements from baseline values were observed in QOL and pain VAS in both groups (p < 0.05). No serious AEs were reported. Conclusion: The between-group similarity of overall treatment satisfaction and effectiveness scores and between-group difference in satisfaction with the utility of the self-injection device was useful information for real-world treatment of osteoporosis. Both medication regimens were well tolerated. [ABSTRACT FROM AUTHOR]

Fracture healing is a complex biological process orchestrated by a delicate interplay of cellular and molecular mechanisms. While the majority of fractures heal spontaneously with appropriate treatment, challenging cases, such as atrophic nonunion, may require adjunctive therapies to achieve successful bone regeneration. In recent years, teriparatide has gained attention as a promising bone-forming agent with the potential to enhance fracture healing and improve clinical outcomes. Preclinical studies using animal models of bone injury have provided evidence supporting the efficacy of teriparatide in promoting fracture healing and resolving nonunion. Histological and radiological findings show that teriparatide enhances callus formation, accelerates bone remodeling, improves biomechanical properties, and reduces the incidence of healing complications. These preclinical results highlight the potential of teriparatide as a therapeutic agent for managing atrophic nonunion in clinical practice. However, further research is necessary to address the limitations of current studies and to establish evidence-based guidelines for the use of teriparatide in nonunion management. [ABSTRACT FROM AUTHOR]

The activins–follistatins–inhibins (AFI) hormonal system affects bone metabolism. Treatments that alter bone metabolism may also alter the AFI molecules. In this non-randomized, open-label, head-to-head comparative study, circulating levels of the AFI system were evaluated in postmenopausal women with osteoporosis treated for 12 mo with either teriparatide (n = 23) or denosumab (n = 22). Τeriparatide treatment increased activin B (P=.01) and activin AB (P=.004) and the ratios activin A/follistatin (P=.006), activin B/follistatin (P=.007), activin AB/follistatin (P<.001), and activin AB/ follistatin-like 3 (FSTL3) (P=.034). The significant P for trend in group × time interactions of activins B and AB and of the ratio activin AB/FSTL3 remained robust after adjustment for BMI and LS BMD but it was lost for activin B after adjustment for previous antiresorptive treatment. The effect of teriparatide on BMD was attenuated when it was adjusted for baseline activins levels or their 12-mo changes. No changes were observed after denosumab treatment. In conclusion, activins B and AB, as well as the ratios of all activins to follistatin and of activin AB to FSTL3 increased with teriparatide treatment, possibly in a compensatory manner. Future studies are needed to study the potentially important role activins may play in bone biology and any associations with the effect of teriparatide on BMD. Clinical Trials identifier: NCT04206618. ClinicalTrials.gov  https://clinicaltrials.gov/search?term=NCT04206618. Lay Summary: Bone and the muscle comprise 2 tissues that are considered to interact with each other, not only through mechanical but also through endocrine signals. Several components of the activins–follistatins–inhibins (AFI) hormonal system have been shown to be secreted by the muscle and affect the bone possibly contributing to this interplay. We have previously investigated the levels of the AFI molecules in case–control studies and reported differences between osteoporotic vs osteopenic vs postmenopausal and premenopausal women with normal BMD. In this 12-mo, non-randomized, open-labeled, head-to-head comparative study, we prospectively compared the effect of antiosteoporotic agents with opposite effect on bone metabolism, that is, teriparatide vs denosumab, on the circulating concentrations of all known molecules of the AFI system in postmenopausal women with osteoporosis. We observed increases of activins after teriparatide treatment, but no effect after denosumab treatment on any of the AFI molecules studied. Since activins are mainly acting in an autocrine way and since activin B and AB have not been extensively studied, further studies in the basic research, preclinical, and clinical research fields are required to expand these observations and fully elucidate physiology and any therapeutic potential. [ABSTRACT FROM AUTHOR]

Context Hypoparathyroidism is a rare disorder characterized by a deficiency in PTH resulting in hypocalcemia, hyperphosphatemia, and hypercalciuria. Eneboparatide is an investigational peptide agonist of the PTH1 receptor for the treatment of chronic hypoparathyroidism (HP). Objective To evaluate the efficacy, safety, and tolerability of eneboparatide in HP patients. Design Open-label, phase 2 study. Participants Twenty-eight patients (21 women, 7 men), mean age (range): 58 years (28-72), with HP were enrolled into 2 consecutive cohorts (C1, n = 12 and C2, n = 16). Intervention Following an optimization period, daily subcutaneous injections of eneboparatide were administered for 3 months at a 20 µg/day (C1) or 10 µg/day (C2) starting dose. Conventional therapy was progressively removed, and eneboparatide could be titrated up to 60 µg (C1) or 80 µg (C2). Main outcomes Proportion of patients achieving independence from conventional therapy, albumin-adjusted serum calcium (ADsCa), 24-h urine calcium (uCa), serum bone turnover markers (serum carboxy-terminal telopeptide of type I collagen and procollagen 1 intact N-terminal propeptide), bone mineral density (BMD), and adverse events (AEs). Results After 3 months, ≥ 88% of patients achieved independence from conventional therapy while mean ADsCa was maintained within target range (7.8-9 mg/dL). Eneboparatide induced a rapid and sustained reduction of mean 24-hour uCa, even among patients with hypercalciuria. Bone turnover markers slightly increased, and BMD remained unchanged, consistent with progressive resumption of physiologic bone turnover. Eneboparatide was well tolerated with no serious AEs. Conclusion Eneboparatide allowed independence from conventional therapy and maintenance of serum calcium within a target range while normalizing uCa excretion and producing a balanced resumption of bone turnover. [ABSTRACT FROM AUTHOR]

Background/Objective: Atypical femur fractures (AFFs) caused by long-term bisphosphonate use are associated with high rates of delayed healing and nonunion. Case Report: A 64-year-old woman with osteopenia on alendronate for 15 years sustained a displaced left AFF following a fall from standing height. Imaging showed an acute displaced transverse diaphyseal left femur fracture with lateral cortical thickening and beaking. She underwent an open reduction and internal fixation with insertion of a cephalomedullary nail placed in compression mode, utilizing a novel technique involving intraoperative removal of the endosteal hypertrophied cortical bone at the fracture site. Alendronate was stopped and teriparatide was initiated postoperatively. Radiographs at 3.5 months postsurgery showed evidence of normal fracture union with mature callus formation. Discussion: AFFs caused by prolonged bisphosphonate use have a high rate of delayed healing and nonunion due to abnormal bone remodeling. Use of teriparatide postoperatively has been shown to reduce healing time in small observational studies in surgically treated patients. Our case demonstrates an expedited healing time of 3.5 months using teriparatide combined with a novel surgical technique involving removal of a portion of the abnormally remodeled bone and placement of an intramedullary nail in compression mode. Conclusion: Our case demonstrates an expedited healing time of 3.5 months compared to the average reported healing time for AFF of 10.7 months, supporting the use of the combination of teriparatide and a novel surgical technique.

Objective: The aim of the study was to evaluate the efficacy and safety of teriparatide compared to other treatments for postmenopausal osteoporosis. Methods: A review of studies from 2000 to January 2023 analyzed randomized controlled trials on postmenopausal women treated with teriparatide (PTH 1–34), comparing it to placebo or other osteoporosis treatments. The analysis focused on bone mineral density (BMD), bone turnover markers, and clinical outcomes, employing Review Manager 5.4.1 and the RoB 2 tool for bias assessment. Results: Our analysis of 23 randomized controlled trials (RCTs) found that PTH (134) treatment significantly increased lumbar spine BMD (mean difference (MD) = 0.02, 95% CI: 0.01–0.03) and femoral neck BMD (MD = 0.01, 95% CI: 0.00–0.01). However, there were no significant changes in total hip and radial bone BMD among the 3536 and 2046 participants, respectively. We also found that PTH (1–34) increased P1NP in a larger cohort (n = 1415) when compared to osteocalcin (n = 206). Although the risk of adverse events increased (relative risk (RR) = 1.65, 95% CI: 1.32–2.07), the incidence of fractures decreased significantly (RR = 0.57, 95% CI: 0.45–0.072), with no significant difference observed in mortality rates between treatment and control groups. Conclusion: Teriparatide improves lumbar spine and femoral neck BMD in postmenopausal women. Particularly notable is the novel finding regarding its effect on radius BMD, an area less explored in previous research. Despite an uptick in adverse events, the marked decrease in fracture incidence confirms its clinical utility for high-risk osteoporosis patients, highlighting the necessity for ongoing investigations into its full skeletal effects.

Summary: This study compared the effectiveness and cardiovascular safety of romosozumab and teriparatide. The main finding was that there were no significant differences between the two drugs in fracture prevention and risk of major adverse cardiac events. This suggests that romosozumab and teriparatide are comparable options for treating osteoporosis. Purpose: This study aimed to determine the preventive effects of romosozumab versus teriparatide on fractures and the risk of cardiovascular events in patients initiating these drugs. Methods: We conducted an active comparator, a new user cohort design, with confounding controlled by inverse probability of treatment weighting using a Japanese administrative claims database (March 2019 to October 2022). This cohort study included 49,104 patients aged 50 years or older who initiated romosozumab (n = 16,125) or teriparatide (n = 32,979) for osteoporosis. The study exposure was the initiation of romosozumab or teriparatide. Effectiveness outcomes were nonvertebral fracture and hip fracture. The safety outcome was major adverse cardiac events (MACE). Follow-up period was 365 days. Results: The weighted incidence rate difference (IRD) for nonvertebral fracture between romosozumab versus teriparatide was –0.08 (95% confidence interval [CI], –0.34 to 0.17) events per 100 person-years (weighted hazard ratio [HR], 0.95 [95% CI, 0.81 to 1.12]); weighted IRD for hip fracture was 0.00 (95% CI, –0.16 to 0.16) events per 100 person-years (weighted HR, 0.99 [95% CI, 0.76 to 1.29]); and weighted IRD for MACE was –0.06 (95% CI, –0.20 to 0.09) events per 100 person-years (weighted HR, 0.90 [95% CI, 0.68 to 1.19]). Conclusion: In patients with osteoporosis, there was no significant difference in the prevention of nonvertebral fracture and hip fracture between romosozumab and teriparatide. In addition, the risk of MACE was comparable between the two drugs. [ABSTRACT FROM AUTHOR]

Summary: The association of renal function with fracture incidence during teriparatide or alendronate treatment in elderly Japanese women was examined. Fracture incidence differed by fracture type, renal function, and treatment protocol. The results provide important information on pharmacotherapy in clinical practice for osteoporosis. Purpose: Incidence rate of morphometric vertebral fracture was lower under treatment with once-weekly teriparatide (TPTD) followed by alendronate (ALN) than under treatment with ALN throughout the study among elderly Japanese women at high fracture risk in JOINT-05. This is an exploratory subgroup analysis according to chronic kidney disease (CKD) status at baseline. Methods: Participants received sequential therapy with TPTD for 72 weeks, followed by ALN for 48 weeks (TPTD-ALN group, N = 483) or ALN monotherapy for 120 weeks (ALN group, N = 496). Baseline CKD status was classified by the estimated glomerular filtration rate (eGFR) and categorized as: CKD 1/2 (eGFR ≥ 60 mL/min/1.73 m2), CKD 3a (eGFR 45–59 mL/min/1.73 m2), or CKD 3b/4 (eGFR < 45 mL/min/1.73 m2). Incidences of vertebral fractures including morphometric fractures, non-vertebral fractures, and all fractures were evaluated during follow-up. Results: Baseline characteristics were not different between treatment groups. Higher stages of CKD were associated with age and number of prevalent vertebral fracture. In CKD 1/2 patients (N = 556 with 90 incidents of morphometric vertebral fracture), the incidence of vertebral fractures was lower in the TPTD-ALN group than in the ALN group (p = 0.01). In CKD 3b/4 patients (N = 112 with 10 incidents of non-vertebral fracture), the incidence of non-vertebral fractures was lower in the ALN group than in the TPTD-ALN group, although the number of fractures was small. In the ALN group, the incidences of vertebral fractures, non-vertebral fractures, and all fractures remained constant across CKD stages. Conclusion: This exploratory analysis showed that fracture incidence on ALN was constant regardless of renal function. It also suggested that the incidence of vertebral fractures on TPTD-ALN was lower than ALN monotherapy in CKD 1/2 patients. These results provide important information for drug selection in the clinical practice of osteoporosis. [ABSTRACT FROM AUTHOR]

Summary: A retrospective analysis comparing a teriparatide biosimilar (RGB-10) with reference teriparatide for osteoporosis treatment in postmenopausal women at high fracture risk found them to be therapeutically equivalent. Both provided significant improvements in lumber spine BMD, TBS, and other parameters of bone health, assessed using multiple diagnostic methods. Purpose: To compare the therapeutic efficacy of a teriparatide biosimilar (RGB-10) with reference teriparatide for the treatment of osteoporosis in postmenopausal women at very high fracture risk. Methods: A retrospective analysis of 25 postmenopausal female patients treated for osteoporosis with RGB-10 for 24 months and a matched cohort of 25 patients treated with reference teriparatide. The following outcomes were assessed at baseline, 12 and 24 months: bone mineral density (BMD) at the lumbar spine, femoral neck and total hip using dual-energy x-ray absorptiometry (DXA) and integral, trabecular and cortical volumetric and surface BMD using 3D-SHAPER® imaging, trabecular bone score (TBS), quantitative ultrasound (QUS) measurements, and high-resolution peripheral quantitative computed tomography (HRpQCT) imaging of the radius and tibia. Results: No significant differences were observed between treatment groups in any of the measured parameters of BMD or bone health at baseline as well as in any timepoint when assessed using these various diagnostic methods. Both compounds provided equivalent significant improvements from baseline in measures of osteoporosis and fracture risk. Conclusion: The results of the analysis demonstrate the therapeutic equivalence of the teriparatide biosimilar (RGB-10) to reference teriparatide for the treatment of osteoporosis in postmenopausal women at very high risk of fracture. [ABSTRACT FROM AUTHOR]

Background/Objective: Teriparatide, an osteoanabolic agent similar to parathyroid hormone in properties, is used to manage severe osteoporosis. Aortic valve stenosis is a common valve condition observed in the elderly. Its natural history includes gradual progression toward severity. We present a case of a patient who had rapidly progressive aortic stenosis after teriparatide initiation. Case Report: An 84-year-old woman who was diagnosed with osteoporosis was treated with oral bisphosphonates. When she had spinal compression fractures, she was found to have primary hyperparathyroidism. She underwent parathyroidectomy and was treated with denosumab infusions every 6 months. However, after she experienced bilateral atypical femoral fractures, she was switched to teriparatide daily injections. Her laboratory test results showed a calcium level of 10 mg/dL (reference range, 8.5-10.2 mg/dL), 25-hydroxyvitamin D level of 38.2 ng/mL (reference range, 31.0-80.0 ng/mL), and phosphorus level of 3.3 mg/dL (reference, range, 2.7-4.8 mg/dL). On reviewing echocardiograms before and after teriparatide initiation, we found a rapid progression of her aortic stenosis from moderate to severe based on the mean gradients (23 to 40 mm Hg) and peak velocities (3.09 to 4 m/s), over a span of 10 months. She eventually required valve replacement. Discussion: Natural progression of mild to severe aortic stenosis typically occurs at the rate of 3 to 7 mm Hg per year over several years. Chronic exposure of human valvular endothelial cells to parathyroid hormone can trigger endothelial dysfunction and valvular calcification. Conclusion: In patients with preexisting aortic stenosis, coordination of care with cardiology and echocardiographic monitoring while on therapy may be considered.

Objective We investigated the clinical efficacy of anabolic agents compared with bisphosphonates (BPs) for the incidence of new osteoporotic vertebral fracture (OVF) and fracture healing of OVF in the patients with OVF via meta-analyses of randomized controlled trials (RCTs). Methods Electronic databases, including PubMed, Embase, and Cochrane Library were searched for published RCTs till December 2022. The RCTs that recruited participants with osteoporosis at high-/very high-risk of fracture (a history of osteoporotic vertebral or hip fracture) or fresh OVF were included in this study. We assessed the risk of bias on every included RCTs, estimated relative risk (RR) for the incidence of new OVF and fracture healing of OVF, and overall certainty of evidence. Meta-analyses were performed by Cochrane review manager (RevMan) ver. 5.3. Cochrane risk of bias 2.0 and GRADEpro/GDT were applied for evaluating methodological quality and overall certainty of evidence, respectively. Results Five hundred eighteen studies were screened, and finally 6 eligible RCTs were included in the analysis. In the patients with prevalent OVF, anabolic agents significantly reduced the incidence of new OVF (teriparatide and romosozumab vs. alendronate and risedronate [RR, 0.57; 95% confidence interval, 0.45–0.71; p < 0.00001; high-certainty of evidence]; teriparatide vs. risedronate [RR, 0.50; 95% confidence interval, 0.37–0.68; p < 0.0001; high-certainty of evidence]). However, there was no evidence of teriparatide compared to alendronate in fracture healing of OVF (RR, 1.23; 95% confidence interval, 0.95–1.60; p = 0.12; low-certainty of evidence). Conclusion In the patients with prevalent OVF, anabolic agents showed a significant superiority for preventing new OVF than BPs, with no significant evidence for promoting fracture healing of OVF. However, considering small number of RCTs in this study, additional studies with large-scale data are required to obtain more robust evidences.

Background: Teriparatide is approved for osteoporosis. Post-marketing surveillance is critical given its widespread use. Objective: To investigate adverse events (AEs) associated with teriparatide using the FAERS database, compare association strengths for key AEs, and explore potential applications to provide clinical reference. Methods: FAERS data from 2004 to 2023 were analyzed. Reports where teriparatide was the primary suspect drug were included. Adverse events were mapped to System Organ Classes and Preferred Terms. Disproportionality analysis using ROR, PRR, BCPNN and EBGM algorithms was conducted to detect safety signals. Results: Out of 107,123 reports with teriparatide as the primary suspect, key AEs identified included pain in extremity (PRR: 4.54), muscle spasms (PRR: 5.11), fractures (PRR range: 17.67-552.95), and increased calcium levels (PRR: 50.73). Teriparatide exhibited a stronger association with increased calcium levels (PRR: 50.73) compared to fractures (PRR range: 17.67-552.95). Notably, only 10.86% of AE reports were submitted by physicians and another 10% by other health professionals. Subset analyses showed a higher consistency of reported AEs from health professionals compared to the general dataset. Off-label uses were noted in conditions such as arthritis (0.57%) and cancer (0.12%). For osteoporosis, main AEs were pain (18.2%), fractures (12.4%), muscle spasms (7.7%), and nausea (6.5%), while glucocorticoid-induced osteoporosis AEs included fractures (24.1%), pain (13.2%), decreased bone density (9.8%), and nausea (5.1%). Conclusion: Our findings provide real-world safety data on teriparatide, revealing key AEs and their association strengths. The low proportion of reports by healthcare professionals suggests the need for cautious interpretation. Continuous vigilance and further research are imperative to guide teriparatide's clinical use. [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]

Bisphosphonates are widely used for the treatment of postmenopausal osteoporosis; however, they cause several long-term side effects, necessitating the investigation of local ways to improve osseointegration in compromised bone tissue. The purpose of this study was to evaluate peri-implant bone repair using implants functionalized with zoledronic acid alone (OVX ZOL group, n = 11), zoledronic acid + teriparatide (OVX ZOL + TERI group, n = 11), and zoledronic acid + ruterpy (OVX ZOL + TERPY group, n = 11) compared to the control group (OVX CONV, n = 11). Analyses included computer-assisted microtomography, qualitative histologic analysis, and real-time PCR analysis. Histologically, all functionalized surfaces improved peri-implant repair, with the OVX ZOL + TERI group standing out. Similar results were found in computerized microtomography analysis. In real-time PCR analysis, however, the OVX ZOL and OVX ZOL + TERPY groups showed better results for bone formation, with the OVX ZOL + TERPY group standing out, while there were no statistical differences between the OVX CONV and OVX ZOL + TERI groups for the genes studied at 28 postoperative days. Nevertheless, all functionalized groups showed a reduced rate of bone resorption. In short, all surface functionalization groups outperformed the control group, with overall better results for the OVX ZOL + TERI group. [ABSTRACT FROM AUTHOR]

Bone forming agents, also known as anabolic therapies, are essential in managing osteoporosis, particularly for patients at very high-risk of fractures. Identifying candidates who will benefit the most from these treatments is crucial. For example, this group might include individuals with severe osteoporosis, multiple vertebral fractures, a recent fragility fracture or those unresponsive to antiresorptive treatments. Definitions of patients with a very high fracture risk vary across nations, are often based on fracture history, bone mineral density (BMD), and/or fracture risk calculated by FRAX® or other algorithms. However, for very high-risk patients, anabolic agents such as teriparatide, abaloparatide, or romosozumab are commonly recommended as first-line therapies due to their ability to stimulate new bone formation and improve bone microarchitecture, offering significant benefits in rapid fracture reduction over antiresorptive therapies. The cost-effectiveness of these agents is a critical consideration for decision-makers. Despite their higher costs, their effectiveness in significantly reducing fracture risk and improving quality of life can justify the investment, especially when long-term savings from reduced fracture rates and associated healthcare costs are considered. Additionally, after completing a course of anabolic therapy, transitioning to antiresorptive agents like bisphosphonates or denosumab is crucial to maintain the gains in bone density and minimize subsequent fracture risks. This sequential treatment approach ensures sustained protection and optimal resource utilization. In summary, the effective use of bone forming agents in osteoporosis requires a comprehensive strategy that includes accurate patient identification, consideration of cost-effectiveness, and implementation of appropriate sequential treatments, ultimately maximizing patient outcomes and healthcare efficiency. [ABSTRACT FROM AUTHOR]

Objective To investigate the difference in the efficacy of sequent teriparatide with denosumab and sequent teriparatide with zoledronic acid in the treatment of osteoporosis in patients with osteoporotic vertebral compression fracture after percutaneous vertebroplasty. Methods A retrospective selection was conducted on 60 postmenopausal osteoporosis patients who underwent percutaneous vertebroplasty at the Nanjing First Hospital from December 2020 to December 2023 and were treated with terlipide for 12 months postoperatively. According to the sequential medication situation， the patients were divided into the denosumab group and the zoledronic acid group，with 30 cases in each group. The changes of serum P1NP，serum β-CTX，lumbar spine BMD，hip BMD and the occurrence of refracture were compared between the two groups before treatment， at 6th month and at 12th month，and the differences of curative effect between the two groups were evaluated. Results The BMD growth rate of hip in the denosumab group was higher than that in the zoledronic acid group after 12 months of treatment (P<0.05). The BMD of lumbar spine and hip in the two groups at 12th month was higher than that before treatment (P<0.05). The BMD of lumbar spine in the denosumab group and the zoledronic acid group at 12th month was 8.7 % and 6.7 % higher than that before treatment， respectively. The BMD of hip in the denosumab group and the zoledronic acid group at 12th month was 6.6 % and 2.9 % higher than that before treatment，respectively. The levels of serum P1NP and serum β-CTX in the denosumab group were lower than those in the zoledronic acid group at 6th month and at 12th month (P<0.05). There was no significant difference in the incidence of refracture between the two groups during treatment (P>0.05). Conclusion In postmenopausal osteoporosis patients with OVCF，teriparatide sequent with denosumab is more effective than sequent with zoledronic acid in increasing bone mineral density in the hip and reducing bone metabolism markers. The two treatment regimens have no significant effect on the incidence of recurrent fractures. [ABSTRACT FROM AUTHOR]

Objective • To evaluate the anti-fracture effect and adverse effects of teriparatide versus bisphosphonate on postmenopausal osteoporosis. This study will provide evidence-based practice for the clinical selection of more effective and safer drugs for these patients. Methods • We searched PubMed, Embase, and the Cochrane Library from database inception to July 2022. The keywords included “fracture”; “teriparatide”, “bisphosphonate”, “postmenopausal women”, and “osteoporosis”. Randomized controlled trials (RCTs) comparing teriparatide versus bisphosphonates on the risk of fracture and adverse effects in postmenopausal osteoporosis were included in the analysis. Results • Finally, 3376 participants were recruited in all 5 RCTs. The results revealed that teriparatide could decrease the rate of clinical vertebral fracture (OR=1.97, 95% CI=1.43-2.73, I² = 0%, P < .0001) and new vertebral fractures (OR=2.44, 95% CI=1.70-3.50, I² = 0%, P < .00001) compared with bisphosphonate. AE results refer to the type and frequency of adverse effects related to drug treatment. The rate of treatment discontinuous due to AEs (OR=0.63, 95% CI=0.48-0.83, I² = 44%, P = .0009) with teriparatide was significantly greater than that with bisphosphonate. However, there was no significant difference in the incidence of adverse events to death (OR=0.59, 95% CI=0.30-1.18, I² = 0%, P = .13). The proportion of patients reporting adverse events in the teriparatide versus bisphosphonate groups was consistent across subgroups, except for the rate of dizziness (OR=0.53, 95% CI=0.31-0.90, I² = 49%, P = .02). Conclusions • Among postmenopausal women with osteoporosis, clinical vertebral fractures and new vertebral fractures decreased more in patients receiving teriparatide than in those receiving bisphosphonate. Although there were no differences in adverse events across subgroups, patients receiving teriparatide had a higher rate of dizziness than those receiving bisphosphonate. The results of this work will provide a reference for clinicians to select appropriate anti-osteoporosis drugs by comprehensively considering individual differences such as fracture risk and dizziness tolerance. [ABSTRACT FROM AUTHOR]

Teriparatide is a peptide derived from a parathyroid hormone (PTH) and an osteoporosis therapeutic drug with potent bone formation‐promoting activity. To identify novel druggable genes that act downstream of PTH signaling and are potentially involved in bone formation, we screened PTH target genes in mouse osteoblast‐like MC3T3‐E1 cells. Here we show that Gprc5a, encoding an orphan G protein‐coupled receptor, is a novel PTH‐inducible gene and negatively regulates osteoblast proliferation and differentiation. PTH treatment induced Gprc5a expression in MC3T3‐E1 cells, rat osteosarcoma ROS17/2.8 cells, and mouse femurs. Induction of Gprc5a expression by PTH occurred in the absence of protein synthesis and was mediated primarily via the cAMP pathway, suggesting that Gprc5a is a direct target of PTH signaling. Interestingly, Gprc5a expression was induced additively by co‐treatment with PTH and 1α, 25‐dihydroxyvitamin D3 (calcitriol), or retinoic acid in MC3T3‐E1 cells. Reporter analysis of a 1 kb fragment of human GPRC5A promoter revealed that the promoter fragment showed responsiveness to PTH via the cAMP response element, suggesting that GPRC5A is also a PTH‐inducible gene in humans. Gprc5a knockdown promoted cell viability and proliferation, as demonstrated by MTT and BrdU assays. Gprc5a knockdown also promoted osteoblast differentiation, as indicated by gene expression analysis and mineralization assay. Mechanistic studies showed that Gprc5a interacted with BMPR1A and suppressed BMP signaling induced by BMP‐2 and constitutively active BMP receptors, ALK2 (ACVR1) Q207D and ALK3 (BMPR1A) Q233D. Thus, our results suggest that Gprc5a is a novel gene induced by PTH that acts in an inhibitory manner on both cell proliferation and osteoblast differentiation and is a candidate for drug targets for osteoporosis. [ABSTRACT FROM AUTHOR]

Endogenous hydrogen sulfide (H 2 S) plays an important role in bone metabolism. However, the exact role of H 2 S in intestinal calcium and phosphorus absorption and its potential in preventing and treating primary osteoporosis remains unknown. Therefore, this study aimed to investigate the potential of H 2 S in promoting intestinal calcium and phosphorus absorption and alleviating primary osteoporosis. We measured the apparent absorptivity of calcium, femoral bone density, expression and sulfhydration of the duodenal endoplasmic reticulum protein of 57 kDa (ERp57), duodenal cystathionine γ-lyase (CSE) expression, and serum H 2 S content in adult and old CSE-knockout and wild-type mice. We also assessed intracellular reactive oxygen species (ROS) and Ca2+ content in CSE-overexpressing or knockout intestinal epithelial cell (IEC)-6 cells. In senile mice, CSE knockout decreased endogenous H 2 S, ERp57 sulfhydration, and intestinal calcium absorption and worsened osteoporosis, which were partially reversed by GYY4137, an H 2 S donor. CSE overexpression in IEC-6 cells increased ERp57 sulfhydration, protein kinase A and C activity, and intracellular Ca2+, whereas CSE knockout exerted the opposite effects. Furthermore, hydrogen peroxide (H 2 O 2) stimulation had similar effects as in CSE knockout, which were reversed by pretreatment with sodium hydrosulfide before H 2 O 2 stimulation and restored by DL-dithiothreitol. These findings suggest that H 2 S attenuates primary osteoporosis by preventing ROS-induced ERp57 damage in intestinal epithelial cells by enhancing ERp57 activity and promoting intestinal calcium absorption, thereby aiding in developing therapeutic interventions to prevent osteoporosis. • H 2 S attenuates primary osteoporosis by promoting intestinal calcium absorption. • H 2 S enhances ERp57 activity by sulfhydration in intestinal epithelial cells. • Sulfhydration prevents ROS-induced ERp57 damage. [ABSTRACT FROM AUTHOR]

Teriparatide is an anabolic drug sometimes administered to patients who have atypical femoral fracture (AFF). However, whether teriparatide has beneficial effects on bone healing remains uncertain. The present study aimed to analyze the association between teriparatide and bone healing in complete AFF. A total of 59 consecutive cases (58 patients) who underwent intramedullary nailing for complete AFF were categorized based on postoperative use of teriparatide into the non-teriparatide (non-TPTD, n = 34) and teriparatide groups (TPTD, n = 25). Time-to-bone union was evaluated and compared between the two groups. Additionally, multiple regression analysis was performed to evaluate factors affecting time-to-bone union. All participants were women, with a mean age of 77.6 years (range: 62–92). No significant difference in time-to-bone union was found between the non-TPTD and TPTD groups (5.5 months vs. 5.8 months, p = 0.359). Two patients in the non-TPTD group underwent reoperation (p = 0.503) due to failure caused by inadequate fixation, and both achieved bone healing after additional fixation with blocking screws. Multiple regression analysis revealed that the anterior gap of the fracture site postoperatively was a factor affecting time-to-bone union (p = 0.014). The beneficial effect of teriparatide on bone healing in complete AFF could not be confirmed. Additional randomized controlled trials are required. Nonetheless, appropriate techniques, including efforts to reduce the gap on the tensile side during the surgery, are important for reliable bone healing. [ABSTRACT FROM AUTHOR]

Diabetic osteopathy is a frequent complication in patients with type 2 diabetes mellitus (T2DM). The association between T2DM and increased fracture risk has led to study the impact of new antidiabetic drugs on bone metabolism. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are incretin mimetic drugs which have many pleiotropic properties. The relationship between GLP-1RAs and bone is very complex: while in vitro and animal studies have demonstrated a protective effect on bone, human studies are scarce. We led a 12 months longitudinal study evaluating bone changes in 65 patients withT2DM for whom a therapy with GLP-1RAs had been planned. Fifty-four T2DM patients completed the 12-month study period; of them, 30 had been treated with weekly dulaglutide and 24 with weekly semaglutide. One-year therapy with GLP-1RAs resulted in a significant reduction in weight and BMI. Bone mineral density (BMD), bone metabolism, trabecular bone score (TBS), adiponectin, and myostatin were evaluated before and after 12 months of GLP-1RAs therapy. After 12 months of therapy bone turnover markers and adiponectin showed a significant increase, while myostatin values showed a modest but significant reduction. BMD-LS by DXA presented a significant reduction while the reduction in BMD-LS by REMS was not significant and TBS values showed a marginal increase. Both DXA and REMS techniques showed a modest but significant reduction in femoral BMD. In conclusion, the use of GLP-1RAs for 12 months preserves bone quality and reactivates bone turnover. Further studies are needed to confirm whether GLP-1RAs could represent a useful therapeutic option for patients with T2DM and osteoporosis. [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: 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]