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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., Competing Interests: Declarations. Ethics approval and consent to participate: This study was performed in accordance with the Declaration of Helsinki as well as with local ethical requirements. All study subjects gave written consent to participate. Conflicts of interest: P. Hadji: Has received study, educational and travel support from Amgen, Elli Lilly, Gedeon Richter, STADA Arzneimittel AG, Theramex and UCB. L. Kamali: No conflicts of interest relevant to this work. F. Thomasius: Has received honoraria for consulting or lectures from Amgen, Fresenius, Gedeon-Richter, STADA Arzneimittel AG, Theramex and UCB. K. Horas: No conflicts of interest relevant to this work. A. Kurth: Has received fees as a scientific advisor for Amgen, Theramex, Merit Medical, AgNovos, UCB, Image Biopsie Lab and as a lecturer for Amgen, STADA Arzneimittel AG, UCB, Alexion, AgNovos, Hologic. N. Bock: No conflicts of interest relevant to this work., (© 2024. The Author(s).)

The overarching goal of osteoporosis management is to prevent fractures. A goal-directed approach to long-term management of fracture risk helps ensure that the most appropriate initial treatment and treatment sequence is selected for individual patients. Goal-directed treatment decisions require assessment of clinical fracture history, vertebral fracture identification (using vertebral imaging as appropriate), measurement of bone mineral density (BMD), and consideration of other major clinical risk factors. Treatment targets should be tailored to each patient's individual risk profile and based on the specific indication for beginning treatment, including recency, site, number and severity of prior fractures, and BMD levels at the total hip, femoral neck, and lumbar spine. Instead of first-line bisphosphonate treatment for all patients, selection of initial treatment should focus on reducing fracture risk rapidly for patients at very high and imminent risk, such as in those with recent fractures. Initial treatment selection should also consider the probability that a BMD treatment target can be attained within a reasonable period of time and the differential magnitude of fracture risk reduction and BMD impact with osteoanabolic versus antiresorptive therapy. This position statement of the ASBMR/BHOF Task Force on Goal-Directed Osteoporosis Treatment provides an overall summary of the major clinical recommendations about treatment targets and strategies to achieve those targets based on the best evidence available, derived primarily from studies in older postmenopausal women of European ancestry., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research.)

With the aid of a new fracture risk model, the great treatment gap for osteoporosis should be closed. All patients older than 70 years should undergo a diagnostic procedure for osteoporosis. An additional risk threshold (≥ 10% per 3 years for femoral and vertebral fractures) should enable patients with a high risk of fracture to be treated with osteoanabolic agents. The use of osteoanabolic agents makes it necessary to administer antiresorptive drugs afterwards. Due to the low event rate of osteonecrosis of the jaw, the initiation of a specific osteoporosis treatment should not be delayed by prophylactic dental treatment. The adherence to the drug treatment should be improved by an individualized approach on the basis of a cooperation between patients, caregivers, and physicians. A regular assessment of falls, including the timed up and go test should be carried out in patients older than 70 years., (© 2024. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

In September 2023, the guideline on the prophylaxis, diagnosis, and treatment of osteoporosis in postmenopausal women and men was published as a completely revised guideline. The implications for practice include a change in the justifying indication for performing a bone density measurement, the time interval over which the fracture risk is determined, the level and number of therapy thresholds, and the recommendations for the therapeutic approach that are adapted to the individual fracture risk present. Risk assessment for the prediction of spine and hip fractures is essential in the context of osteoporosis diagnostics. In addition to age and gender, there are a total of 33 risk factors to determine the individual risk of fracture. Much more attention is paid to the assessment of the risk of falls and, depending on the result, combined with recommendations for muscle training and protein intake from the age of 65. Risk indicators must also be taken into account when determining the indication for osteoporosis diagnosis, as well as the risk factors of the imminent risk of fracture. The indication for baseline diagnostics has changed from the >20% 10-year fracture risk to diagnostics in postmenopausal women and in men aged 50 years and older, depending on the fracture risk factor profile. This eliminates a specific fracture risk threshold for basic diagnostics. Thus, in the young patient group (50-60 years), the risk factors considered medically relevant for the indication for osteoporosis diagnosis must be taken into account. New thresholds as an indication for initiating therapy is the determination of fracture risk using a risk calculator over 3 years instead of 10 years. The indication for drug therapy should be based on the threshold values of the DVO risk model. The data clearly suggests a significantly faster and more effective fracture risk-reducing effect of anabolic therapy. This is recommended in the first sequence in cases of a very high risk of fracture from 10%/3 years with osteoanabolic active substances (teriparatide or romosozumab). Such a therapy sequence should be initiated directly and not delayed due to upcoming dental procedures. Follow-up therapy to consolidate the reduction of fracture risk should be chosen individually., Competing Interests: Dr. Friederike Thomasius gibt folgende Interessenskonflikte an: Koordinatorin der Leitlinienkommission des DVO. Prof. Dr. Heide Siggelkow gibt folgende Interessenkonflikte an: Mitglied der Leitlinienkommission des DVO., (Thieme. All rights reserved.)

With the aid of a new fracture risk model, the great treatment gap for osteoporosis should be closed. All patients older than 70 years should undergo a diagnostic procedure for osteoporosis. An additional risk threshold (≥ 10% per 3 years for femoral and vertebral fractures) should enable patients with a high risk of fracture to be treated with osteoanabolic agents. The use of osteoanabolic agents makes it necessary to administer antiresorptive drugs afterwards. Due to the low event rate of osteonecrosis of the jaw, the initiation of a specific osteoporosis treatment should not be delayed by prophylactic dental treatment. The adherence to the drug treatment should be improved by an individualized approach on the basis of a cooperation between patients, caregivers, and physicians. A regular assessment of falls, including the timed up and go test should be carried out in patients older than 70 years., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Since 2018, the present S3 guideline Prophylaxis, Diagnosis and Therapy of Osteoporosis (AWMF 183-001) has been updated following a previous update of the underlying PICO questions (Population-Intervention-Comparison-Outcome questions) for a systematic literature search. The focus of the guideline update, in addition to updating the evidence supporting literature along with recommendations, was the development of a risk calculator for vertebral fractures and femoral neck fractures. This is essential for managing risk assessment because of the multitude of risk factors that contribute to fracture risk. This article considers the development of the guideline update methodologically and substantively, the latter by reflecting on the core themes of the guideline update., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Despite 2 h of daily exercise training, muscle wasting and bone loss are still present after 6-month missions to the international space station. Some crew members lose bone much faster than others. In preparation for missions to the Moon and Mars, space agencies are therefore reviewing their countermeasure portfolios. Here, we discuss the potential of current pharmacological strategies. Bone loss in space is fuelled by bone resorption. Alendronate, an oral bisphosphonate, reduced bone losses in experimental bed rest and space. However, gastrointestinal side effects precluded its further utilization in space. Zoledronate (a potent bisphosphonate), denosumab (RANKL antagonist) and romosozumab (sclerostin antagonist) are all administered via injection. They effectively suppress bone resorption and are routinely prescribed against osteoporosis. Their serious adverse effects, namely, osteonecrosis of the jaw and atypical femur fractures occur very rarely when the usage is limited to 1 or 2 years. Hence, utilization of one of these compounds may outweigh the bone risks of space travelling, in particular in those with high bone resorption rates. Muscle wasting in space is likely due to hampered muscle protein synthesis. Even though this might theoretically be countered by the synthesis-boosting effects of anabolic steroids, the practical grounds for such recommendation are currently weak. Moreover, they reveal their full potential only when combined with an anabolic exercise stimulus, for example, via strength training. It therefore seems that a combination of exercise and pharmacological countermeasures should be considered for musculoskeletal health on the way to the Moon and Mars and back., (© 2023 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Exercise is a recognized component in the prevention and therapy of osteoporosis. The present systematic review and meta-analysis aimed to determine the effect of Vitamin D (Vit-D) added to exercise versus exercise alone on bone mineral density (BMD) at the lumbar spine (LS) or hip in older adults. A systematic review based on six literature databases according to PRISMA included (a) exercise trials, with an exercise (EX) and a combined exercise + Vit-D group (EX + Vit-D), (b) intervention ≥ 6 months, and (c) BMD assessments at LS or hip. Effects sizes (MD) and 95%-confidence intervals (95%-CI) were calculated using a random-effect model that includes the inverse heterogeneity model (IVhet). Five studies with 281 participants in the EX and 279 participants in the EX + Vit-D were included. No significant differences between EX versus EX + Vit-D were observed for BMD-LS (MD: 0.002, 95%-CI: -0.033 to 0.036) or BMD-hip (MD: 0.003, 95%-CI: -0.035 to 0.042). Heterogeneity between the trial results was moderate-substantial for LS ( I 2  = 0%) and moderate for hip-BMD ( I 2  = 35%). The funnel plot analysis suggests evidence for a publication/small study bias for BMD-LS and hip results. In summary, this present systematic review and meta-analysis were unable to determine significant positive interaction of exercise and Vit-D on LS- or hip-BMD. We predominately attribute this finding to (1) the less bone-specific exercise protocols of at least two of the five studies and (2) the inclusion criteria of the studies that did not consequently focus on Vit-D deficiency. This issue should be addressed in more detail by adequately powered exercise trials with promising exercise protocols and participants with Vit-D deficiency. This trial is registered with the International Prospective Register of Systematic Reviews (PROSPERO) ID: CRD42022309813., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Cecilie Fischer et al.)

This narrative review summarises the recommendations of a Working Group of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) for the conduct and reporting of real-world evidence studies with a focus on osteoporosis research., Purpose: Vast amounts of data are routinely generated at every healthcare contact and activity, and there is increasing recognition that these real-world data can be analysed to generate scientific evidence. Real-world evidence (RWE) is increasingly used to delineate the natural history of disease, assess real-life drug effectiveness, understand adverse events and in health economic analysis. The aim of this work was to understand the benefits and limitations of this type of data and outline approaches to ensure that transparent and high-quality evidence is generated., Methods: A ESCEO Working Group was convened in December 2022 to discuss the applicability of RWE to osteoporosis research and approaches to best practice., Results: This narrative review summarises the agreed recommendations for the conduct and reporting of RWE studies with a focus on osteoporosis research., Conclusions: It is imperative that research using real-world data is conducted to the highest standards with close attention to limitations and biases of these data, and with transparency at all stages of study design, data acquisition and curation, analysis and reporting to increase the trustworthiness of RWE study findings., (© 2023. The Author(s).)

The aim of this systematic review and meta-analysis was (1) to determine exercise effects on bone mineral density (BMD) in postmenopausal women and (2) to address the corresponding implication of bone and menopausal status or supervision in postmenopausal women. A comprehensive search of eight electronic databases according to the PRISMA statement up to August 9, 2022, included controlled exercise trials ≥ 6 months. BMD changes (standardized mean differences: SMD) at the lumbar spine (LS), femoral neck (FN), and total hip (TH) were considered as outcomes. Study group comparisons were conducted for osteopenia/osteoporosis versus normal BMD, early versus late postmenopausal women, and predominantly supervised versus predominantly non-supervised study arms. We applied an inverse heterogeneity (IVhet) model. In summary, 80 studies involving 94 training and 80 control groups with a pooled number of 5581 participants were eligible. The IVhet model determined SMDs of 0.29 (95% CI: 0.16-0.42), 0.27 (95% CI: 0.16-0.39), and 0.41 (95% CI: 0.30-0.52) for LS, FN, and THBMD, respectively. Heterogeneity between the trial results varied from low (I 2 = 20%, TH BMD) to substantial (I 2 = 68%, LS-BMD). Evidence for publication bias/small study effects was negligibly low (FN-, TH-BMD) to high (LSBMD). We observed no significant differences (p > .09) for exercise effects on LS-, FN-, or TH-BMD-LS between studies/study arms with or without osteopenia/osteoporosis, early versus late postmenopausal women, or predominantly supervised versus non-supervised exercise programs. Using robust statistical methods, the present work provides further evidence for a positive effect of exercise on BMD in postmenopausal women. Differences in bone status (osteopenia/osteoporosis versus normal bone), menopausal status (early versus late postmenopausal), and supervision (yes versus no) did not significantly affect the exercise effects on BMD at LS or proximal femur., (© 2023. The Author(s).)

The study results indicate that women with osteoporosis initiated on gastro-resistant risedronate have a lower risk of fracture than those initiated on immediate release risedronate or alendronate. A large proportion of women discontinued all oral bisphosphonate therapies within 1 year of treatment start., Purpose: Using a US claims database (2009-2019), we compared risk of fractures between women with osteoporosis initiated on gastro-resistant (GR) risedronate and those initiated on (a) immediate release (IR) risedronate or (b) immediate release alendronate., Methods: Women aged ≥ 60 years with osteoporosis who had ≥ 2 oral bisphosphonate prescription fills were followed for ≥ 1 year after the first observed bisphosphonates dispensing (index date). Fracture risk was compared between the GR risedronate and IR risedronate/alendronate cohorts using adjusted incidence rate ratios (aIRRs), both overall and in subgroups with high fracture risk due to older age or comorbidity/medications. Site-specific fractures were identified based on diagnosis codes recorded on medical claims using a claims-based algorithm. Persistence on bisphosphonate therapy was evaluated for all groups., Results: aIRRs generally indicated lower fracture risk for GR risedronate than IR risedronate and alendronate. When comparing GR risedronate to IR risedronate, statistically significant aIRRs (p < 0.05) were observed for pelvic fractures in the full cohorts (aIRRs = 0.37), for any fracture and pelvic fractures among women aged ≥ 65 years (aIRRs = 0.63 and 0.41), for any fracture and pelvic fractures among women aged ≥ 70 years (aIRRs = 0.69 and 0.24), and for pelvic fracture among high-risk women due to comorbidity/medications (aIRR = 0.34). When comparing GR risedronate to alendronate, statistically significant aIRRs were observed for pelvic fractures in the full cohorts (aIRR = 0.54), for any fracture and wrist/arm fractures among women aged ≥ 65 years (aIRRs = 0.73 and 0.63), and for any fracture, pelvic, and wrist/arm fractures among women aged ≥ 70 years (aIRRs = 0.72, 0.36, and 0.58). In all cohorts, ~ 40% completely discontinued oral bisphosphonates within 1 year., Conclusions: Discontinuation rates of oral bisphosphonate therapy were high. However, women initiated on GR risedronate had a significantly lower risk of fracture for several skeletal sites than women initiated on IR risedronate/alendronate, particularly those aged ≥ 70 years., (© 2023. The Author(s).)

Objectives: Due to their pronounced anti-inflammatory and immunosuppressive effects, glucocorticoids (GCs) are widely used in inflammatory conditions and organ transplants. Unfortunately, GC-induced osteoporosis is one of the most common causes of secondary osteoporosis. The aim of the present systematic review and meta-analysis was to determine the effect of exercise added to GC therapy on BMD at the lumbar spine or femoral neck in people on GC therapy., Methods: A systematic literature search of five electronic databases included controlled trials with a duration of >6 months and at least two study arms [glucocorticoids (GCs) and GCs and exercise (GC + EX)] were conducted up to 20 September 2022. Studies involving other pharmaceutical therapies with relevant effects on bone metabolism were excluded. We applied the inverse heterogeneity model. Outcome measures were standardized mean differences (SMDs) with 95% CIs for BMD changes at the lumbar spine (LS) and femoral neck (FN)., Results: We identified three eligible trials with a total of 62 participants. In summary, the GC + EX intervention indicated statistically significantly higher SMDs for LS-BMD [SMD 1.50 (95% CI 0.23, 2.77)] but not for FN-BMD [0.64 (95% CI -0.89, 2.17)] compared with GC treatment alone. We observed substantial heterogeneity (LS-BMD I 2  = 71%, FN-BMD I 2  = 78%) between the study results., Conclusion: Although more well-designed exercise studies are needed to address the issue of exercise effects on GC-induced osteoporosis (GIOP) in more detail, upcoming guidelines should pay more attention to the aspect of exercise for bone strengthening in GIOP., Registration Number: PROSPERO: CRD42022308155., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

The role of exercise in preventing osteoporotic fractures is vague, and further recommendations for optimized exercise protocols are very rare. In the present work, we provided positive evidence for exercise effects on the number of osteoporotic fractures in adults, albeit without observing any significant relevance of intensity progression or study duration., Introduction: Osteoporotic fractures are a major challenge confronting our aging society. Exercise might be an efficient agent for reducing osteoporotic fractures in older adults, but the most promising exercise protocol for that purpose has yet to be identified. The present meta-analysis thus aimed to identify important predictors of the exercise effect on osteoporotic fractures in adults., Methods: We conducted a systematic search of six literature databases according to the PRISMA guideline that included controlled exercise studies and reported the number of low-trauma major osteoporotic fractures separately for exercise (EG) and control (CG) groups. Primary study outcome was incidence ratio (IR) for major osteoporotic fractures. Sub-analyses were conducted for progression of intensity (yes vs. no) during the trial and the study duration (≤ 12 months vs. > 12 months)., Results: In summary, 11 studies with a pooled number of 9715 participant-years in the EG and 9592 in the CG were included. The mixed-effects conditional Poisson regression revealed positive exercise effects on major osteoporotic fractures (RR: 0.75, 95% CI: 0.54-0.94, p = .006). Although studies with intensity progression were more favorable, our subgroup analysis did not determine significant differences for diverging intensity progression (p = .133) or study duration (p = .883). Heterogeneity among the trials of the subgroups (I 2  ≤ 0-7.1%) was negligible., Conclusion: The present systematic review and meta-analysis provided significant evidence for the favorable effect of exercise on major osteoporotic fractures. However, diverging study and exercise characteristics along with the close interaction of exercise parameters prevented the derivation of reliable recommendations for exercise protocols for fracture reductions., Prospero Id: CRD42021250467., (© 2022. The Author(s).)

The purpose of this systematic review and meta-analysis (PROSPERO ID: CRD42021250467) was to evaluate the effects of exercise on low-trauma overall and major osteoporotic fractures (hip, spine, forearm, or humerus fractures) and to determine the corresponding effect of supervision of the exercise program. Our systematic search of six literature databases according to the PRISMA guideline was conducted from January 1, 2013 (ie, date of our last search) to May 22, 2021, and included controlled clinical exercise trials with (i) individuals aged ≥45 years, (ii) cohorts without therapies/diseases related to fractures, (iii) observation periods of ≥3 months, and (iv) the number of low-trauma fractures listed separately for the exercise (EG) and control (CG) groups. We included 20 intervention studies with 21 EGs and 20 CGs comprising a pooled number of participant-years of n = 11.836 in the EG and n = 11.275 in the CG. The mixed-effects conditional Poisson regression revealed significant effects of exercise on low-trauma overall incidence (rate) ratio (IR 0.67, 95% confidence interval [95% CI] 0.51-0.87) and major osteoporotic fractures IR (0.69, 95% CI 0.52-0.92). Heterogeneity between the trials was moderate for low-trauma overall (I2 = 40%) and negligible (I2 < 1%) for major osteoporotic fractures. Supervision of the exercise program plays a significant role in the reductions of overall and major osteoporotic fractures with IR about twice as favorable in the predominately supervised (IR 0.44; 95% CI 0.27-0.73 and 0.38; 0.19-0.76) versus the predominately non-supervised exercise trials (IR 0.83; 95% CI 0.60-1.14 and 0.82; 0.64-1.05). In summary, the present study provides evidence for the positive effect of exercise on low-trauma overall and major osteoporotic fractures in middle aged to older adults. Supervision of the exercise program is a crucial aspect in exercise programs on fracture reduction. Thus, home-based exercise protocols should increasingly implement online classes to ensure widely consistent supervision and monitoring of the exercise program. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)., (© 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).)

Oral bisphosphonates are a key intervention in the treatment of osteoporosis and in reducing the risk of fragility fractures. Their use is supported by over 3 decades of evidence; however, patient adherence to oral bisphosphonates remains poor in part due to complex dosing instructions and adverse events, including upper gastrointestinal symptoms. This problem has led to the development of novel oral bisphosphonate formulations. Buffered, effervescent alendronate is dissolved in water and so seeks to reduce upper gastro-intestinal adverse events, and gastro-resistant risedronate aims to reduce the complexity of dosing procedure (e.g. fasting prior to consumption) whilst still maintaining the efficacy of fracture risk reduction. Clinical trials and real-world data have been employed to demonstrate some benefits in terms of reduced upper gastro-intestinal adverse events, adherence, persistence and health economic outcomes. This report describes the result of an ESCEO (European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis) expert working group, which explores where oral bisphosphonates sit in current clinical practice guidelines, review their risk-benefit profile and the consequences of poor adherence before exploring novel oral bisphosphonate formulations and their potential clinical and health economic impact. Further research is required but there are signs that these novel, oral bisphosphonate formulations may lead to improved tolerance of oral bisphosphonates and thus, improved adherence and fracture outcomes., (© 2022. The Author(s).)

Context: There is some evidence that an adequate "anabolic hormonal milieu" is essential for the mechanosensitivity/transduction/response of bone tissue., Objective: This work aimed to determine whether enhancing hormone therapy (HT) with exercise increases the isolated effect of HT on bone mineral density (BMD) at the lumbar spine (LS) and femoral neck (FN)., Methods: A comprehensive search of 6 electronic databases according to the PRISMA statement up to April 28, 2021, included controlled trials longer than 6 months with 3 study arms: (a) HT, (b) exercise, and (c) HT plus exercise (HT + E). Apart from HT, no pharmaceutic therapy or diseases with relevant osteoanabolic or osteocatabolic effect on bone metabolism were included. The present analysis was conducted as a random-effects meta-analysis. Outcome measures were standardized mean differences (SMD) for BMD changes at the LS and FN., Results: Our search identified 6 eligible studies (n = 585). Although the effect of HT + E was more pronounced in the LS (SMD: 0.19; 95% C,: -0.15 to 0.53) and FN-BMD (0.18; -0.09 to 0.44) compared to the HT group, we did not observe significant differences between the 2 groups. We observed a low (I2: 29%) or moderate (I2: 49%) level of heterogeneity between the trials for FN or LS., Conclusion: We do not observe a significant effect of HT + E vs HT alone. We largely attribute this result to varying HT supplementation and hormonal status. Bearing in mind that synergistic/additive effects between HT and mechanical stimulation can only be expected in situations of hormonal insufficiency, further clinical studies should consider baseline endogenous estrogen production but also HT dosing more carefully., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Osteoporosis care has evolved markedly over the last 50 years, such that there are now an established clinical definition, validated methods of fracture risk assessment and a range of effective pharmacological agents. Currently, bone-forming (anabolic) agents, in many countries, are used in those patients who have continued to lose bone mineral density (BMD), patients with multiple subsequent fractures or those who have fractured despite treatment with antiresorptive agents. However, head-to-head data suggest that anabolic agents have greater rapidity and efficacy for fracture risk reduction than do antiresorptive therapies. The European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) convened an expert working group to discuss the tools available to identify patients at high risk of fracture, review the evidence for the use of anabolic agents as the initial intervention in patients at highest risk of fracture and consider the sequence of therapy following their use. This position paper sets out the findings of the group and the consequent recommendations. The key conclusion is that the current evidence base supports an "anabolic first" approach in patients found to be at very high risk of fracture, followed by maintenance therapy using an antiresorptive agent, and with the subsequent need for antiosteoporosis therapy addressed over a lifetime horizon., (© 2022. The Author(s).)

Patients with osteoporosis prescribed risedronate gastro-resistant had a lower incidence of fractures versus those prescribed other oral bisphosphonates. Administration of risedronate gastric-resistant does not require fasting, and this more convenient dosing administration may explain its improved efficacy., Purpose: Up to half of patients do not follow complex dosing instructions of immediate-release bisphosphonates used for the prevention of osteoporotic fractures, which can result in suboptimal effectiveness. Risedronate gastro-resistant (GR) offers a more convenient dosing option by eliminating the need for fasting. This study compares fracture rates and outcomes between osteoporosis women treated with risedronate GR (GR cohort) versus other oral bisphosphonates (other cohort)., Methods: Claims from women with osteoporosis in the USA were analyzed. Patients were classified into the two cohorts based on the first oral bisphosphonate observed (index date) and matched 1:1 based on patient characteristics. Patients were observed for ≥ 2 years following the index date. Fracture rates, health care resource utilization and costs, and treatment persistence were compared., Results: In total, 2,726 patients were selected in each cohort (median age: 60.0 years). The incidence of fractures was lower in the GR versus the other cohort for any fracture sites (incidence rate ratio, 95% CI: 0.83, 0.70-0.97) and spine fractures (0.71, 0.54-0.95), although the respective rate of medication discontinuation at 2 years was 80.5% and 74.4%. Time to first fracture was delayed for the GR cohort, reaching statistical significance after 36 months. The GR cohort incurred fewer hospitalizations (incidence rate per 1,000 patient-years: GR = 106.74; other = 124.20, p < 0.05) translating into lower hospitalization costs per patient per year (GR = $3,611; other = $4,603, p < 0.05)., Conclusions: Patients prescribed risedronate GR versus other bisphosphonates had a lower incidence of fractures, which may be explained by the fact that the GR formulation is absorbed even when taken with food., (© 2021. The Author(s).)

Exercise frequency is a key aspect of exercise protocols. In this systematic review and meta-analysis, we determined the effect of training frequency on (areal) bone mineral density (BMD) at lumbar spine (LS) and hip. Reviewing seven electronic databases up to April 2021, we conducted a systematic review of the literature according to the PRISMA statement. Inclusion criteria were (a) controlled exercise trials (b) with at least two study arms that compared low versus high exercise frequency, (c) an intervention ≥6 months and (d) BMD assessments at lumbar spine (LS) or hip. The analysis was conducted as a mixed-effect meta-analysis and used "type of exercise" and "study duration" as moderators in subgroup analyses. Standardized mean differences (SMD) for LS- and hip-BMD changes were defined as outcome measures. Seven studies with 17 exercise groups were included in the analysis. We observed significantly higher effects of high (≥2 sessions/week) vs. low net training frequency (1-<2 sessions/week) exercise on LS- (SMD 0.55, 95%-CI: 0.20-0.90) but not hip-BMD (0.19, -0.06 to 0.45). Study duration was found to be a significant moderator for the effect of training frequency at LS- but not hip-BMD. In parallel, the type of exercise moderately influences the effect of training frequency on LS- but not on hip-BMD. We observed a superior effect of higher net training frequency on BMD. Longer exercise exposition increases this effect. Considering e.g. holidays, indisposition or other temporary absence, exercise programs on osteoporosis should provide at least 3 sessions/week/year to allow a net training frequency of more than two sessions/week. STUDY REGISTRATION: PROSPERO (CRD42021246804)., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Fracture risk cannot be determined by bone density alone. It is important to identify and consider risk factors that individually increase the risk of fractures when they occur. Risk calculators have been developed worldwide to determine fracture risk. The risk factors currently listed in the Dachverbands Osteologie (DVO) S3 Guidelines for the "Diagnosis and Therapy of Postmenopausal Osteoporosis and Male Osteoporosis" are diverse and should be prioritized, since not every fracture risk factor present increases the risk of a vertebral or femoral neck fracture to the same extent. Due to the unknown interaction between risk factors, no more than two risk factors in addition to age, gender, and bone density measurement should be considered per patient. For risk assessment, it is important that the two thresholds defined by the German guideline are reached, above which diagnostic workup or specific therapy for fracture risk reduction should be recommended. These thresholds are currently defined as 20% for diagnostics and 30% for therapy, based on the absolute 10-year risk for vertebral and femoral neck fractures. The threshold for diagnostics is reached with the presence of a risk factor mentioned in the guideline. To reach the threshold for therapy, the bone density measurement result is required to reach the age-specific T‑score. However, typical fragile fractures of the vertebral bodies or femur increase the fracture risk so substantially that therapy can be recommended even without a bone density result.

Update on fracture prevention after menopause Abstract. Osteoporosis is a common disease. It is multifactorial and polygenetic in pathogenesis as well as clinically underdiagnosed and undertreated. There are several medical specialties involved in the care of female osteoporosis patients. "Gate keepers" of all female osteoporosis patients are the gynecologists, because they see the patient at the onset of menopausal symptoms, which may be indicative of accelerated bone loss. It is important to plan therapy with different sequences, one of which may be gynecologically recommended hormone therapy. Since osteoporosis is a chronic disease in the vast majority of cases, long-term therapy and patient retention is essential.

This study assessed the deconditioning hypothesis of low back pain (LBP) by examining physical function in relation to LBP and self-reported physical activity in women. This cross-sectional study recruited a representative population-based sample of females aged greater than 60 years. In total, 1182 women were included in the study and completed questionnaires (physical activity and LBP intensity) and functional testing (countermovement jump, chair rise, gait speed and grip strength). Individuals were stratified into four groups based on physical activity and LBP status and analysed via a two-way ANOVA. Most participants (87%) reported current LBP and 25% were physically active. Countermovement jump height, chair rise and grip strength were lower in physically inactive women ( p  ≤ 0.005), but not women with LBP ( p  ≥ 0.21). Gait speed was not associated with physical activity or LBP status. There was no association between LBP and physical activity status. Whilst LBP was associated with lower physical activity, contrary to the deconditioning hypothesis, LBP status itself was not associated with reduced physical function in community-dwelling women 60 years and older. This implies that LBP may not be related to physical function in this population group, but rather to their physical activity levels.

Since the observations of Fuller Albright in 1940, it is well documented that estrogen deficiency is one of the major causes of osteoporosis. Osteoporosis increases not only the risk of fracture and consecutively the number of fractures but can also induce a disorder of fracture healing. This raises the question whether estrogen deficiency negatively influences bone healing in addition to fragility. The currently available literature on this topic provides indications that estrogen deficiency negatively influences fracture healing in the various stages of healing. Furthermore, there is evidence that the administration of estrogen antagonizes these negative effects. Future clinical investigations are needed to find out whether the experimental data can be transferred to the patients.

Purpose: Premenopausal women receiving chemotherapy or endocrine treatment for early breast cancer are at increased risk for cancer treatment induced bone loss (CTIBL). The aim of the randomized, double-blind ProBONE II trial was to investigate whether a 2-year adjuvant treatment with 4 mg intravenous zoledronic acid (ZOL) every 3 months versus placebo would prevent CTIBL after a five-year period., Methods: Thirty-one of the 34 participants in the ZOL arm and thirty-four of the 36 participants in the placebo arm were followed-up to the 5-year visit and completed the study as planned. The changes in Bone Mass Density (BMD) were assessed at baseline and each visit after treatment initiation., Results: After 24 months, BMD at the lumbar spine showed a 2.9% increase in patients treated with ZOL vs. a 7.1% decrease in placebo-treated participants compared to baseline (p < 0.001). Over the 60-month study period, we found a decrease of 2.2% vs. 7.3% in the BMD at the lumbar spine in patients receiving ZOL and placebo respectively (p < 0.001). Over the 60-month study period, BMD in the placebo arm showed a continuous decrease at all sites (p < 0001), whereas patients treated with ZOL reached baseline BMD-values at the femoral neck and total hip., Conclusions: In ProBone II, a 2-year treatment with ZOL 4 mg intravenous every 3 months prevented cancer treatment induced bone loss in premenopausal women with breast cancer and maintained the BMD up to 3 years post-treatment., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Introduction/objectives: Preference for supplement formulation helps determine an individual's adherence to long-term medication and can improve clinical benefit for chronic illnesses such as osteoporosis. This study compared the preference, acceptability and tolerability of a reformulation of Calcichew D3 1 500 mg/400 IU and Calcichew D3 500 mg/800 IU (Takeda UK Ltd, Wobrun Green, UK) with Adcal-D3 2 500 mg/400 IU (ProStrakan Ltd, Galashiels, UK) and Kalcipos-D 500 mg/800 IU (Meda Pharmaceuticals Ltd, Bishop's Stortford, UK), respectively., Method: This phase IV, randomized, open-label, two-period, cross-over study was conducted at nine sites in the UK and Germany. Eligible subjects (≥65 years requiring calcium/vitamin D supplementation for prevention/treatment of deficiencies, or ≥18 years requiring supplementation as an adjunct to osteoporosis treatment) were randomly assigned to one of two 2 week treatment sequences - Group 1: Calcichew D3 500/400 then Adcal-D3 500/400 (or vice versa), or Group 2: Calcichew D3 500/800 then Kalcipos-D 500/800 (or vice versa). After each treatment period, patients rated the treatment for acceptability using 100 mm visual analogue scales. After the second treatment period, patients indicated their treatment preference. The primary endpoint, the percentage of patients with a preference for each treatment, was analyzed with a logistic regression model., Results: Two hundred and seventy-six patients were randomly assigned by treatment sequence, 138 to each group. Preference questionnaires among patients who preferred Calcichew or comparator revealed the odds for patients preferring Calcichew 500/400 (77.6%) over Adcal-D3 was 3.46 ([95% CI 2.24, 5.36], p < 0.001) in Group 1, and Calcichew D3 500/800 (63.2%) over Kalcipos-D was 1.72 ([1.19, 2.47], p = 0.004) in Group 2. Adverse events were mostly gastrointestinal and were comparable between groups. The new formulation of Calcichew D3 is acceptable and consistent with its known tolerability profile., Conclusions: In this short-term 30 day study, patients preferred Calcichew D3 500/400 and Calcichew D3 500/800 over respective comparators. A trend towards better compliance with Calcichew D3 preference observed in Group 1 warrants a longer term study to identify treatment compliance., Trial Registration: Clinicaltrials.gov: NCT02457247.

Data on treatment of glucocorticoid-induced osteoporosis (GIO) in men are scarce. We performed a randomized, open-label trial in men who have taken glucocorticoids (GC) for ≥3 months, and had an areal bone mineral density (aBMD) T-score ≤ -1.5 standard deviations. Subjects received 20 μg/d teriparatide (n = 45) or 35 mg/week risedronate (n = 47) for 18 months. Primary objective was to compare lumbar spine (L1 -L3 ) BMD measured by quantitative computed tomography (QCT). Secondary outcomes included BMD and microstructure measured by high-resolution QCT (HRQCT) at the 12th thoracic vertebra, biomechanical effects for axial compression, anterior bending, and axial torsion evaluated by finite element (FE) analysis from HRQCT data, aBMD by dual X-ray absorptiometry, biochemical markers, and safety. Computed tomography scans were performed at 0, 6, and 18 months. A mixed model repeated measures analysis was performed to compare changes from baseline between groups. Mean age was 56.3 years. Median GC dose and duration were 8.8 mg/d and 6.4 years, respectively; 39.1% of subjects had a prevalent fracture, and 32.6% received prior bisphosphonate treatment. At 18 months, trabecular BMD had significantly increased for both treatments, with significantly greater increases with teriparatide (16.3% versus 3.8%; p = 0.004). HRQCT trabecular and cortical variables significantly increased for both treatments with significantly larger improvements for teriparatide for integral and trabecular BMD and bone surface to volume ratio (BS/BV) as a microstructural measure. Vertebral strength increases at 18 months were significant in both groups (teriparatide: 26.0% to 34.0%; risedronate: 4.2% to 6.7%), with significantly higher increases in the teriparatide group for all loading modes (0.005 < p < 0.015). Adverse events were similar between groups. None of the patients on teriparatide but five (10.6%) on risedronate developed new clinical fractures (p = 0.056). In conclusion, in this 18-month trial in men with GIO, teriparatide showed larger improvements in spinal BMD, microstructure, and FE-derived strength than risedronate., (Copyright © 2013 American Society for Bone and Mineral Research.)

Objective: To examine in a major cohort of patients whether or not musculoskeletal adverse effects (MAEs), similar to those seen in intravenous bisphosphonates (BP), might occur also in high dosage oral treatment regimens with alendronate (ALN) and risedronate (RSN)., Patients and Methods: 612 consecutive patients treated in the osteoporosis outpatient clinic at Charite, Campus Benjamin Franklin, between July 2002 and October 2003 with oral ALN or RSN (mean age 68.2+/-9.7 years; 527 females, 85 males), were examined and followed up for MAEs., Results: The overall frequency of any severe MAEs in our patients was low (5.6%). All severe MAEs occurred in primarily once weekly treated patients: 27 in ALN 70 mg once weekly (27/134=20.1%) and 7 in RSN 35 mg once weekly (7/28=25.0%), with no significant difference between those groups. The most frequently reported MAE was acute arthralgia in 12.6%, followed by acute back pain in 9.1% of all primarily once weekly treated cases. None of the 302 patients initially treated with daily BP reported any MAEs when later switching to once weekly administration (218 patients to ALN 70 mg once weekly and 84 patients to RSN 35 mg once weekly). With reference to recently published data, the phenomenon is probably related to dose dependent gammadelta T cell activation by accumulation of isopentenyl pyrophosphate (IPP) due to inhibition of the mevalonate pathway by nitrogen containing bisphosphonates (nBP)., Conclusions: MAEs in oral BP are, in general, less common and severe than in intravenous BP. They are observed exclusively in patients starting ALN or RSN treatment with once weekly dosage regimens. In order to avoid this phenomenon, it is suggested to start ALN or RSN treatment with the lower daily dosages of ALN 10 mg daily or RSN 5 mg daily for about two weeks before switching to the overall, more convenient, once weekly dose regimen.