Achieving osteoporosis treat-to-target goals with teriparatide or alendronate: sub-analysis of Japanese Osteoporosis Intervention Trial-05 (JOINT-05).

INTRODUCTION: The purpose of this study was to evaluate whether bone mineral density (BMD) ≥ -2.5 SD could be used as the treat-to-target (T2T) goal when treating osteoporosis with teriparatide (TPTD) and alendronate (ALN), and to investigate the relationship with incident vertebral fracture by re-analyzing data from a randomized, controlled trial (JOINT-05) involving postmenopausal Japanese women at high fracture risk. MATERIALS AND METHODS: Participants received sequential therapy with once-weekly TPTD for 72 weeks, followed by ALN for 48 weeks (TPTD-ALN group) or ALN monotherapy for 120 weeks (ALN group). BMDs were measured at the lumbar spine (L2-4), total hip, and femoral neck at 0, 24, 48, 72, and 120 weeks by dual-energy X-ray absorptiometry. The T2T goal was BMD ≥ -2.5 SD, and the endpoint was the proportion of participants with baseline BMD < -2.5 SD in three measurement sites achieving BMD ≥ -2.5 SD. RESULTS: A total of 559 participants were selected. BMD ≥ -2.5 SD at 120 weeks in the L2-4, total hip, and femoral neck sites was achieved in 20.5%, 23.1%, and 5.9%, respectively, in the TPTD-ALN group and 22.2%, 11.7%, and 7.3%, respectively, in the ALN group. Incident vertebral fractures occurred in areas of both lower and high BMD. CONCLUSION: During the 1.5-year treatment period, more than 20% of participants achieved BMD ≥ -2.5 SD as a T2T goal at L2-4. Since the achievement level differed depending on the BMD measurement site, the appropriate site should be selected according to the baseline BMD level.

The positive impact of smoking cessation on fracture risk in a nationwide cohort study.

Many studies sought to demonstrate the association between smoking and fracture risk. However, the correlation between smoking and fractures remains controversial. This study aimed to examine the impact of smoking and smoking cessation on the occurrence of fractures using prospective nationwide cohort data. We enrolled those who underwent a National Health Insurance Service (NHIS) health checkup in 2009-2010 who had a previous health checkup 4-year prior (2005-2006). The study population of 4,028,559 subjects was classified into three groups (non-smoker, smoking cessation, current smoker). The study population was also analyzed according to fracture type (all fractures, vertebral fracture, hip fracture). Lastly, the smoking cessation group and current smoker group were divided into four subgroups based on a lifetime smoking amount cut-off of 20 pack-years (PY). Multivariate-adjusted hazard ratios (HRs) of fracture were examined through a Cox proportional hazards model. After multivariable adjustment, non-smokers showed the lowest risk of fracture (HR = 0.818, CI 0.807-0.828, p < 0.0001) and smoking cessation significantly lowered the risk of fracture (HR 0.938, 95% CI 0.917-0.959, p < 0.0001) compared to current smokers. Regardless of 20PY, all smoking cessation subgroups showed significantly less risk of fractures than current smokers with ≥ 20PYs. Smoking increases the risk of fracture, and smoking cessation lowers the risk of fracture.

Etidronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women.

BACKGROUND: Osteoporosis is an abnormal reduction in bone mass and bone deterioration, leading to increased fracture risk. Etidronate belongs to the bisphosphonate class of drugs which act to inhibit bone resorption by interfering with the activity of osteoclasts - bone cells that break down bone tissue. This is an update of a Cochrane review first published in 2008. For clinical relevance, we investigated etidronate's effects on postmenopausal women stratified by fracture risk (low versus high). OBJECTIVES: To assess the benefits and harms of intermittent/cyclic etidronate in the primary and secondary prevention of osteoporotic fractures in postmenopausal women at lower and higher risk of fracture, respectively. SEARCH METHODS: We searched the Cochrane Central Register of Control Trials (CENTRAL), MEDLINE, Embase, two clinical trial registers, the websites of drug approval agencies, and the bibliographies of relevant systematic reviews. We identified eligible trials published between 1966 and February 2023. SELECTION CRITERIA: We included randomized controlled trials that assessed the benefits and harms of etidronate in the prevention of fractures for postmenopausal women. Women in the experimental arms must have received at least one year of etidronate, with or without other anti-osteoporotic drugs and concurrent calcium/vitamin D. Eligible comparators were placebo (i.e. no treatment; or calcium, vitamin D, or both) or another anti-osteoporotic drug. Major outcomes were clinical vertebral, non-vertebral, hip, and wrist fractures, withdrawals due to adverse events, and serious adverse events. We classified a study as secondary prevention if its population fulfilled one or more of the following hierarchical criteria: a diagnosis of osteoporosis, a history of vertebral fractures, a low bone mineral density T-score (≤ -2.5), or aged 75 years or older. If none of these criteria were met, we considered the study to be primary prevention. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. The review has three main comparisons: (1) etidronate 400 mg/day versus placebo; (2) etidronate 200 mg/day versus placebo; (3) etidronate at any dosage versus another anti-osteoporotic agent. We stratified the analyses for each comparison into primary and secondary prevention studies. For major outcomes in the placebo-controlled studies of etidronate 400 mg/day, we followed our original review by defining a greater than 15% relative change as clinically important. For all outcomes of interest, we extracted outcome measurements at the longest time point in the study. MAIN RESULTS: Thirty studies met the review's eligibility criteria. Of these, 26 studies, with a total of 2770 women, reported data that we could extract and quantitatively synthesize. There were nine primary and 17 secondary prevention studies. We had concerns about at least one risk of bias domain in each study. None of the studies described appropriate methods for allocation concealment, although 27% described adequate methods of random sequence generation. We judged that only 8% of the studies avoided performance bias, and provided adequate descriptions of appropriate blinding methods. One-quarter of studies that reported efficacy outcomes were at high risk of attrition bias, whilst 23% of studies reporting safety outcomes were at high risk in this domain. The 30 included studies compared (1) etidronate 400 mg/day to placebo (13 studies: nine primary and four secondary prevention); (2) etidronate 200 mg/day to placebo (three studies, all secondary prevention); or (3) etidronate (both dosing regimens) to another anti-osteoporotic agent (14 studies: one primary and 13 secondary prevention). We discuss only the etidronate 400 mg/day versus placebo comparison here. For primary prevention, we collected moderate- to very low-certainty evidence from nine studies (one to four years in length) including 740 postmenopausal women at lower risk of fractures. Compared to placebo, etidronate 400 mg/day probably results in little to no difference in non-vertebral fractures (risk ratio (RR) 0.56, 95% confidence interval (CI) 0.20 to 1.61); absolute risk reduction (ARR) 4.8% fewer, 95% CI 8.9% fewer to 6.1% more) and serious adverse events (RR 0.90, 95% CI 0.52 to 1.54; ARR 1.1% fewer, 95% CI 4.9% fewer to 5.3% more), based on moderate-certainty evidence. Etidronate 400 mg/day may result in little to no difference in clinical vertebral fractures (RR 3.03, 95% CI 0.32 to 28.44; ARR 0.02% more, 95% CI 0% fewer to 0% more) and withdrawals due to adverse events (RR 1.41, 95% CI 0.81 to 2.47; ARR 2.3% more, 95% CI 1.1% fewer to 8.4% more), based on low-certainty evidence. We do not know the effect of etidronate on hip fractures because the evidence is very uncertain (RR not estimable based on very low-certainty evidence). Wrist fractures were not reported in the included studies. For secondary prevention, four studies (two to four years in length) including 667 postmenopausal women at higher risk of fractures provided the evidence. Compared to placebo, etidronate 400 mg/day may make little or no difference to non-vertebral fractures (RR 1.07, 95% CI 0.72 to 1.58; ARR 0.9% more, 95% CI 3.8% fewer to 8.1% more), based on low-certainty evidence. The evidence is very uncertain about etidronate's effects on hip fractures (RR 0.93, 95% CI 0.17 to 5.19; ARR 0.0% fewer, 95% CI 1.2% fewer to 6.3% more), wrist fractures (RR 0.90, 95% CI 0.13 to 6.04; ARR 0.0% fewer, 95% CI 2.5% fewer to 15.9% more), withdrawals due to adverse events (RR 1.09, 95% CI 0.54 to 2.18; ARR 0.4% more, 95% CI 1.9% fewer to 4.9% more), and serious adverse events (RR not estimable), compared to placebo. Clinical vertebral fractures were not reported in the included studies. AUTHORS' CONCLUSIONS: This update echoes the key findings of our previous review that etidronate probably makes or may make little to no difference to vertebral and non-vertebral fractures for both primary and secondary prevention.

The Safety and Efficacy of Abaloparatide on Postmenopausal Osteoporosis: A Systematic Review and Meta-analysis.

PURPOSE: The aging of the population increases the incidence of postmenopausal osteoporosis, which threatens the health of elderly women. Abaloparatide is a synthetic peptide analogue of the human parathyroid hormone-related protein that has recently been approved for the treatment of postmenopausal osteoporosis. Its efficacy and safety have not been systematically evaluated. Therefore, studies on the efficacy and safety of abaloparatide could be of assistance in the clinical medication of postmenopausal osteoporosis. The aim of this study was to evaluate the clinical efficacy and safety of abaloparatide in postmenopausal osteoporosis. METHODS: PubMed, Cochrane Library, EMBASE, and Web of Science databases were electronically searched from inception to July 6, 2023, for relevant randomized controlled trials. Two review authors independently conducted the study screening, quality assessment (based on the Risk of Bias Assessment Tool recommended in the Cochrane handbook), and data extraction. Outcome measures included bone mineral density (BMD), bone turnover and metabolic markers, incidence of fractures, and adverse events. Data analyses were processed by using Stata SE15. FINDINGS: Ultimately, 8 randomized controlled trials, involving a total of 3705 postmenopausal women, were included. Meta-analysis showed that abaloparatide administration significantly increased the BMD of the lumbar vertebrae (standardized mean difference [SMD], 1.28 [95% CI, 0.81-1.76); I2 = 78.5%]), femoral neck (SMD, 0.70 [95% CI, 0.17-1.23; I2 = 75.7%]), and hip bone (SMD, 0.86 [95% CI, 0.53-1.20; I2 = 60.4%]) in postmenopausal women compared with the control group. Type I procollagen N-terminal propeptide, a bone formation marker, was also elevated after abaloparatide administration. The incidence of vertebral fracture was lower in the abaloparatide group than in the control group (risk ratio, 0.13; 95% CI, 0.06-0.26; I2 = 0%). There was no significant difference in the incidence of adverse events between the abaloparatide and the placebo groups (risk ratio, 1.03; 95% CI, 0.99-1.06; I2 = 0%). IMPLICATIONS: Abaloparatide has a protective effect on women with postmenopausal osteoporosis. It could reduce their risk for vertebral fracture; increase their BMD of the lumbar spine, femoral neck, and hip; and alleviate symptoms and complications of postmenopausal osteoporosis with considerable safety. Limitations of this study include not searching the gray literature and not performing a subgroup analysis. PROSPERO Registration No.: CRD42022370944.

An online clinical decision tool to screen for vertebral fragility fractures (Vfrac) in older women presenting with back pain in general practice: protocol for a feasibility study in preparation for a future cluster randomised controlled trial.

This feasibility study for a future definitive randomized trial assesses the use and acceptability of a new clinical decision tool to identify risk of a vertebral fracture and those who should be referred for spinal radiography in women aged 65 or over presenting to primary care with back pain. PURPOSE: Approximately 12% of older adults have vertebral fragility fractures, but currently fewer than one-third are diagnosed, potentially limiting access to bone protection treatment. Vfrac is a vertebral fracture screening tool which classifies individuals into high or low risk of having a vertebral fracture, allowing targeting of spinal radiographs to high-risk individuals. The objective of this study was to investigate the feasibility of conducting a cluster randomized controlled trial to evaluate the use of an online version of Vfrac in primary care. METHODS: The study will run in six general practices, with three given the Vfrac tool for use on older women (> 65 years) consulting with back pain and three using standard clinical processes for managing such back pain. Anonymised data covering a 12-month period will be collected from all sites on consultations by older women with back pain. Focus groups will be undertaken with healthcare professionals and patients on whom the tool was used to understand the acceptability of Vfrac and identify factors that impact its use. These patients will be sent a paper version of the Vfrac questionnaire to self-complete at home. Outputs of the self-completion Vfrac (high versus low risk) will be compared with the face-to-face Vfrac (high versus low risk), and agreement assessed using Cohen's kappa. RESULTS: This study will evaluate the use and acceptability of Vfrac within primary care and determine if data on resource use can be collected accurately and comprehensively. CONCLUSIONS: This article describes the protocol of the Vfrac feasibility study. TRIAL REGISTRATION: ISRCTN18000119 (registered 01/03/2022) and ISRCTN12150779 (registered 10/01/2022).

[Brittle bones]. / 5 minutes pour apprendre. Des os fragiles.

The use of corticosteroids is common in our clinical practice. Cortico-induced osteoporosis should be taken into consideration when using a dosage higher than 7.5 mg/d of prednisone or equivalent for a minimum of 3 months. We describe the case of a 69-year-old female patient who received long-term corticosteroid treatment for low back pain and developed secondary vertebral compression fractures. This case illustrates the importance of assessing fracture risk when prescribing corticosteroids, in order to offer preventive measures and introduce (in subjects with high risk) prophylactic treatments aiming to reduce the risk of irreversible consequences.

[Development of the new guidelines on osteoporosis : Methodological and content development]. / Entwicklung der neuen Leitlinien Osteoporose : Methodische und inhaltliche Entwicklung.

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.

Cholecalciferol Use Is Associated With a Decreased Risk of Incident Morphometric Vertebral Fractures in Acromegaly.

CONTEXT: Skeletal fragility is observed in 30% to 60% of acromegaly patients, representing an emerging complication of the disease that increases disability. Despite several studies having investigated the clinical and hormonal prognostic factors for the occurrence of vertebral fractures (VFs) in acromegaly, very few data are available on their prevention/treatment including the effect of vitamin D (VD) supplementation, which has been reported to have a fracture-protective effect in several studies in patients with osteoporosis. OBJECTIVE: We aimed to investigate the role of cholecalciferol (D3) supplementation in the prevention of incident VFs (i-VFs) in acromegaly. METHODS: A longitudinal, retrospective and multicenter study was performed on 61 acromegaly patients treated and untreated with D3 supplementation. RESULTS: Twenty-six patients were treated with D3 supplementation according to clinical guidelines. The median D3 weekly dosage was 8500 IU (interquartile range [IQR]: 3900). The median duration of D3 supplementation was 94 months (IQR: 38). At last follow-up, i-VFs were diagnosed in 14 patients (23%). I-VFs were less prevalent in patients on D3 supplementation (14.3% of cases) compared to patients not treated with D3 (85.7%; P = .02). The final level of serum V25OH-D was significantly lower in patients who developed i-VFs (28.6 ng/mL, IQR: 4.1) compared to patients who did not develop i-VFs (34.2 ng/mL, IQR: 9.6; P = .05). The logistic regression confirmed the protective role of D3 supplementation on the occurrence of i-VFs (odds ratio: 0.16; 95% CI, 0.03-0.79; P = .01). CONCLUSION: It is likely that D3 supplementation could lead to a reduction in i-VFs in acromegaly.

Diagnóstico por imagen de las fracturas vertebrales de baja energía / Imaging of low-energy vertebral fractures

Las fracturas vertebrales de baja energía suponen un reto diagnóstico para el radiólogo debido a su naturaleza, frecuentemente inadvertida, y a su semiología en imagen, a menudo sutil. Sin embargo, el diagnóstico de este tipo de fracturas puede resultar determinante, no solo por permitir realizar un tratamiento dirigido que evite complicaciones, sino también por la posibilidad de diagnosticar patologías sistémicas como la osteoporosis o la enfermedad metastásica. El tratamiento farmacológico en el primer caso ha demostrado evitar el desarrollo de otras fracturas y complicaciones, mientras que los tratamientos percutáneos y las diversas terapias oncológicas pueden ser una alternativa en el segundo caso. Por lo tanto, es preciso conocer la epidemiología y los hallazgos por imagen de este tipo de fracturas. El objetivo de este trabajo es revisar el diagnóstico por imagen de las fracturas de baja energía, con especial énfasis en las características que deben reseñarse en el informe radiológico para orientar a un diagnóstico específico que favorezca y optimice el tratamiento de los pacientes que padecen este tipo de fracturas.(AU)

Low-energy vertebral fractures pose a diagnostic challenge for the radiologist due to their often-inadvertent nature and often subtle imaging semiology. However, the diagnosis of this type of fractures can be decisive, not only because it allows targeted treatment to prevent complications, but also because of the possibility of diagnosing systemic pathologies such as osteoporosis or metastatic disease. Pharmacological treatment in the first case has been shown to prevent the development of other fractures and complications, while percutaneous treatments and various oncological therapies can be an alternative in the second case. Therefore, it is necessary to know the epidemiology and typical imaging findings of this type of fractures. The objective of this work is to review the imaging diagnosis of low-energy fractures, with special emphasis on the characteristics that should be outlined in the radiological report to guide a specific diagnosis that favours and optimizes the treatment of patients suffering of low energy fractures.(AU)

Establishment of a novel risk prediction model for recompression of augmented vertebrae at the thoracolumbar junction and modified puncture technique for prevention: a multicenter retrospective study.

OBJECTIVE: Recompression of augmented vertebrae (RCAV) is often seen after percutaneous kyphoplasty (PKP), especially at the thoracolumbar junction. The authors aimed to develop and validate a risk prediction model (nomogram) for RCAV and to evaluate the efficacy of a modified puncture technique for RCAV prevention after PKP for thoracolumbar osteoporotic vertebral fractures (OVFs). METHODS: Patients who underwent PKP for single thoracolumbar OVFs (T10-L2) between January 2016 and October 2020 were reviewed and followed up for at least 2 years. All patients were randomly divided into a training group (70%) and a validation group (30%). Relevant potential data affecting recompression were collected. Predictors were screened by using binary logistic regression analysis to construct the nomogram. Calibration and receiver operating characteristic curves were used to evaluate the consistency of the prediction models. Finally, the efficacy of the modified puncture technique for prevention of RCAV in OVF patients with a preoperative intravertebral cleft (IVC) was further demonstrated through binary logistic regression analysis. RESULTS: Overall, 394 patients were included and 116 of them (29.4%) sustained RCAV. The independent risk factors included decreased bone mineral density, lower level of serum 25-hydroxy vitamin D3, larger C7-S1 sagittal vertical axis (SVA), preoperative IVC, and solid-lump cement distribution. The area under the curve (AUC) of the prediction model was 0.824 in the training group and 0.875 in the validation group patients. The calibration curve indicated the predictive power of this nomogram, with the preoperative IVC having the highest prediction accuracy (AUC 0.705). The modified puncture technique significantly reduced the incidence of RCAV by enhancing bone cement distribution into a sufficiently diffused distribution in OVF patients with preoperative IVC. CONCLUSIONS: The nomogram prediction model had satisfactory accuracy and clinical utility for identification of patients at low and high risk of postoperative RCAV. Patients at high risk of postoperative RCAV might benefit from the target puncture technique and vitamin D supplementation as well as effective antiosteoporotic therapies.

Refracture risk and all-cause mortality after vertebral fragility fractures: Anti-osteoporotic medications matter.

BACKGROUND: Osteoporotic vertebral fractures may predict the future occurrence of fractures and increase mortality. Treating underlying osteoporosis may prevent second fractures. However, whether anti-osteoporotic treatment can reduce the mortality rate is not clear. The aim of this population study was to identify the degree of decreased mortality following the use of anti-osteoporotic medication after vertebral fractures. METHODS: We identified patients who had newly diagnosed osteoporosis and vertebral fractures from 2009 to 2019 using the Taiwan National Health Insurance Research Database (NHIRD). We used national death registration data to determine the overall mortality rate. RESULTS: There were 59,926 patients with osteoporotic vertebral fractures included in this study. After excluding patients with short-term mortality, patients who had previously received anti-osteoporotic medications had a lower refracture rate as well as a lower mortality risk (hazard ratio (HR): 0.84, 95% confidence interval (CI): 0.81-0.88). Patients receiving treatment for more than 3 years had a much lower mortality risk (HR: 0.53, 95% CI: 0.50-0.57). Patients who used oral bisphosphonates (alendronate and risedronate, HR: 0.95, 95% CI: 0.90-1.00), intravenous zoledronic acid (HR: 0.83, 95% CI: 0.74-0.93), and subcutaneous denosumab injections (HR: 0.71, 95% CI: 0.65-0.77) had lower mortality rates than patients without further treatment after vertebral fractures. CONCLUSION: In addition to fracture prevention, anti-osteoporotic treatments for patients with vertebral fractures were associated with a reduction in mortality. A longer duration of treatment and the use of long-acting drugs was also associated with lower mortality.

Extensive expertise in endocrinology: advances in the management of glucocorticoid-induced osteoporosis.

Osteoporosis is a common consequence of long-term oral glucocorticoid therapy and the resulting fractures cause significant morbidity. Bone loss occurs rapidly after initiation of glucocorticoid therapy; the accompanying increase in risk of fracture is dose-dependent and occurs within a few months of starting therapy. The adverse effects of glucocorticoids on bone are mediated by inhibition of bone formation accompanied by an early but transient increase in bone resorption, due both to direct and indirect effects on bone remodelling. Fracture risk assessment should be performed as soon as possible after long-term glucocorticoid therapy (≥3 months) is initiated. FRAX can be adjusted for the dose of prednisolone but does not currently take fracture site, recency, or number into account and therefore may underestimate fracture risk, particularly in individuals with morphometric vertebral fractures. Vertebral fracture assessment should therefore be regarded as a routine part of fracture risk estimation in individuals receiving long-term glucocorticoid therapy. Bone protective therapy should be started promptly in individuals at high-risk, together with calcium and vitamin D supplements. Bisphosphonates are generally regarded as first-line options on the grounds of their low cost, but anabolic therapy should be considered as an alternative first-line option in very high-risk individuals.

Effect of hormone replacement therapy on intervertebral disc height.

OBJECTIVE: Intervertebral discs act as shock absorbers, thereby helping to reduce the risk of vertebral body fractures. Previous studies have shown that estrogen loss following menopause is associated with disc height reduction whereas treatment with hormone replacement therapy (HRT) helps to maintain disc height. This study reports the effect of HRT on disc height from a post hoc analysis of a prospective randomized clinical trial of the effect of HRT on bone density. METHODS: A total of 355 healthy postmenopausal women aged (mean ± standard deviation) 55.4 ± 4.8 years were randomized to HRT with oral 1 mg or 2 mg estradiol plus dydrogesterone or placebo. Dual-energy X-ray absorptiometry measurements (Lunar DPX) were obtained at baseline and following 2 years of treatment. Intervertebral disc height was measured in discs between T12 and L3 using the bone densitometer ruler. RESULTS: Compared with baseline, treatment with HRT resulted in a significant increase in total disc height with 1 mg estradiol (0.16 ± 0.65 cm, p = 0.015) and with 2 mg estradiol (0.21 ± 0.86 cm, p = 0.006) whilst there was no significant increase with placebo (0.13 ± 0.65 cm, p = 0.096). Between-group differences were not statistically significant. CONCLUSIONS: These results are consistent with previous findings of a beneficial effect of estrogen on discs. This may be in part responsible for the anti-fracture efficacy of HRT on vertebral fractures.

The clinical effectiveness of denosumab (Prolia®) in patients with hormone-sensitive cancer receiving endocrine therapy, compared to bisphosphonates, selective estrogen receptor modulators (SERM), and placebo: a systematic review and network meta-analysis.

This systematic review (SR) assessed the use of denosumab (Prolia®) to treat osteoporosis in cancer patients receiving endocrine therapy. Denosumab was found to prevent vertebral fractures and improve bone mineral density in cancer patients with osteoporosis. This is the first SR to assess treating osteoporotic cancer patients with denosumab. PURPOSE: This study assessed the effectiveness and safety of denosumab (Prolia®) compared to bisphosphonates (alendronate, ibandronate, risedronate, zoledronate), selective estrogen receptor modulators (SERMs) (bazedoxifene, raloxifene) and placebo for the treatment of osteoporosis in hormone-sensitive cancer patients receiving endocrine therapy (men with prostate cancer [MPC] on hormone ablation therapy [HAT], and women with breast cancer [WBC] on adjuvant aromatase inhibitor therapy [AAIT]). METHODS: Systematic literature searches were conducted in three biomedical databases to identify randomized controlled trials (RCTs). Frequentist network meta-analyses and/or pairwise meta-analyses were performed on predetermined outcomes (i.e., vertebral/nonvertebral fractures, bone mineral density [BMD], mortality, treatment-related adverse events [AEs], serious AEs [SAEs], withdrawal due to treatment-related AEs). RESULTS: A total of 14 RCTs (15 publications) were included. Denosumab was found to prevent vertebral fractures in cancer patients receiving endocrine therapy, relative to placebo. Similarly, denosumab, zoledronate, and alendronate improved BMD at the femoral neck (FN) and lumbar spine (LS) in MPC on HAT, relative to placebo. Denosumab, ibandronate and risedronate improved BMD at the LS and total hip (TH) in WBC on AAIT, relative to placebo. Denosumab and risedronate improved trochanteric (TRO) BMD in WBC on AAIT, relative to placebo. Similarly, denosumab improved FN BMD in WBC on AAIT. CONCLUSION: In MPC on HAT, denosumab (relative to placebo) was effective at preventing vertebral fractures and improving BMD at the FN and LS. Moreover, in WBC on AAIT, denosumab (relative to placebo) improved BMD at the FN, LS, TH, and TRO, as well as prevent vertebral fracture.

Effectiveness and Safety of Treatments to Prevent Fractures in People With Low Bone Mass or Primary Osteoporosis: A Living Systematic Review and Network Meta-analysis for the American College of Physicians.

BACKGROUND: The prevalence of osteoporosis is increasing in the United States. PURPOSE: To evaluate low bone mass and osteoporosis treatments to prevent fractures. DATA SOURCES: Ovid MEDLINE ALL, Ovid Evidence Based Medicine Reviews: Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and ClinicalTrials.gov from 2014 through February 2022. STUDY SELECTION: Adults receiving eligible interventions for low bone mass or osteoporosis. Randomized controlled trials (RCTs) for fracture outcomes, and RCTs and large observational studies (n ≥1000) for harms. DATA EXTRACTION: Abstracted by 1 reviewer and verified by a second. Independent, dual assessments of risk of bias and certainty of evidence (CoE). DATA SYNTHESIS: We included 34 RCTs (in 100 publications) and 36 observational studies. Bisphosphonates and denosumab reduced hip, clinical and radiographic vertebral, and other clinical fractures in postmenopausal females with osteoporosis (moderate to high CoE). Bisphosphonates for 36 months or more may increase the risk for atypical femoral fractures (AFFs) and osteonecrosis of the jaw (ONJ), but the absolute risks were low. Abaloparatide and teriparatide reduced clinical and radiographic vertebral fractures but increased the risk for withdrawals due to adverse events (WAEs; moderate to high CoE). Raloxifene and bazedoxifene for 36 months or more reduced radiographic vertebral but not clinical fractures (low to moderate CoE). Abaloparatide, teriparatide, and sequential romosozumab, then alendronate, may be more effective than bisphosphonates in reducing clinical fractures for 17 to 24 months in older postmenopausal females at very high fracture risk (low to moderate CoE). Bisphosphonates may reduce clinical fractures in older females with low bone mass (low CoE) and radiographic vertebral fractures in males with osteoporosis (low to moderate CoE). LIMITATION: Few studies examined participants with low bone mass, males, or Black-identifying persons, sequential therapy, or treatment beyond 3 years. CONCLUSION: Bisphosphonates, denosumab, abaloparatide, teriparatide, and romosozumab, followed by alendronate, reduce clinical fractures in postmenopausal females with osteoporosis. Abaloparatide and teriparatide increased WAEs; longer duration bisphosphonate use may increase AFF and ONJ risk though these events were rare. PRIMARY FUNDING SOURCE: American College of Physicians. (PROSPERO: CRD42021236220).

Sequential treatment of teriparatide and alendronate versus alendronate alone for elevation of bone mineral density and prevention of refracture after percutaneous vertebroplasty in osteoporosis: a prospective study.

BACKGROUND: Percutaneous vertebroplasty was the most common strategy for osteoporotic vertebral compression fracture. However, refracture after vertebroplasty also occurred and bone mineral density (BMD) was one of the main factors associated with refracture after percutaneous vertebroplasty. AIMS: To investigate the efficacy of a short-sequential treatment of teriparatide followed by alendronate on prevention of refracture after percutaneous vertebroplasty in osteoporotic patients, and compare it with the therapy of alendronate alone. METHODS: From January 2018 to January 2020, we recruited 165 female osteoporosis patients after percutaneous vertebroplasty who were assigned into sequential treatment of teriparatide followed by alendronate group (TPTD + ALN group) and alendronate alone group (ALN group). The vertebral fracture occurred during this process was also recorded in both the groups. A total of 105 participants completed the 1-year follow-up. Furthermore, BMD and serum procollagen type I N-terminal propeptide (PINP) and C-terminal cross-linking telopeptide of type I collagen (CTX) were compared between the two groups during 1-year follow-up. RESULTS: The 105 patients were finally included, with 59 in ALN group and 46 in TPTD + ALN group. During 1-year follow-up, the vertebral refracture rate in TPTD + ALN group was much lower than that in ALN group (2.2% vs. 13.6%, p < 0.05). At 12 months, the BMDs at lumbar in TPTD + ALN group were significantly elevated when compared to the ALN group (0.65 ± 0.10 vs. 0.57 ± 0.07, p < 0.001). DISCUSSION AND CONCLUSION: A short-sequential administration of teriparatide followed by alendronate was more effective in elevating the BMD and decreasing the refracture rate at 12-month follow-up, compared to the counterpart with alendronate alone.

Effects of hospitalist co-management on rate of initiation of osteoporosis treatment in patients with vertebral compression fractures: Retrospective cohort study.

BACKGROUND: Vertebral compression fractures are common in elderly people and most are due to osteoporosis. Osteoporosis treatment is effective for secondary prophylaxis, so initiation is recommended. Despite the clear benefits, the rate of initiation of osteoporosis treatment is very low. It is reported to be due to several factors including insufficient systems-based approaches for hospitals and post-acute care. Hospitalists, who are physicians dedicated to the treatment of patients in hospital and whose activity is generalist rather than specialized, are reported to be associated with higher-quality inpatient care because of, among other things, closer adherence to guidelines. Co-management by hospitalists for patients with vertebral compression fractures has potential benefits towards improving the outcomes. We compared the rate of initiation of osteoporosis treatment for patients with vertebral compression fractures between conventional orthopedic surgeon-led care (conventional group) and hospitalist co-management care (co-management group). METHODS: This is a single-center retrospective cohort study to evaluate the rate of initiation of osteoporosis treatment and reasons for non-initiation of osteoporosis treatment. Other clinical indicators were also evaluated, including length of hospital stay, preventable complications during hospitalization, and rate of 30-day readmission. RESULTS: We identified 55 patients in the conventional group and 93 patients in the co-management group. The rate of initiation of osteoporosis treatment was higher in the co-management group (45.2% vs. 3.6%, OR 21.5; 95%CI 5.12-192.0; P < 0.01). Most of the patients with non-initiation in the co-management group had reasons for it described in the medical records, but in the conventional group the reasons were unknown. There was no significant difference in length of hospital stay, preventable complications during hospitalization, or 30-day readmission between the groups. CONCLUSIONS: Hospitalist co-management of patients with vertebral compression fractures showed significantly higher rate of initiation of osteoporosis treatment than conventional orthopedic surgeon-led care.

Sequential therapy with once-weekly teriparatide injection followed by alendronate versus monotherapy with alendronate alone in patients at high risk of osteoporotic fracture: final results of the Japanese Osteoporosis Intervention Trial-05.

In this randomized, controlled trial, sequential therapy with once-weekly subcutaneous injection of teriparatide for 72 weeks, followed by alendronate for 48 weeks resulted in a significantly lower incidence of morphometric vertebral fracture than monotherapy with alendronate for 120 weeks in women with osteoporosis at high risk of fracture. PURPOSE: To determine whether the anti-fracture efficacy of sequential therapy with teriparatide, followed by alendronate is superior to that of monotherapy with alendronate, a prospective, randomized, open-label, blinded-endpoint trial was performed. METHODS: Japanese women aged at least 75 years were eligible for the study, if they had primary osteoporosis and if they were at high risk of fracture. Patients were randomly assigned (1:1) to receive the sequential therapy (once-weekly subcutaneous injection of teriparatide 56.5 µg for 72 weeks, followed by alendronate for 48 weeks) or monotherapy with alendronate for 120 weeks. The primary endpoint in the final analysis was the incidence of morphometric vertebral fracture during the 120-week follow-up period. RESULTS: Between October 2014 and June 2020, 505 patients in the sequential therapy group and 506 in the monotherapy group were enrolled. Of these, 489 and 496, respectively, were included in the main analysis. The incidence of morphometric vertebral fracture during the 120-week follow-up period in the sequential therapy group (64 per 627.5 person-years, annual incidence rate 0.1020) was significantly lower than that in the monotherapy group (126 per 844.2 person-years, annual incidence rate 0.1492), with a rate ratio of 0.69 (95% confidence interval 0.54 to 0.88, P < 0.01). After 72 weeks, no patient had a severe adverse event that was considered related to the study drug. CONCLUSION: Once-weekly injection of teriparatide, followed by alendronate resulted in a significantly lower incidence of morphometric vertebral fracture than alendronate monotherapy in women with osteoporosis who were at high risk of fracture. TRIAL REGISTRATION NUMBER, DATE OF REGISTRATION: jRCTs031180235 and UMIN000015573, March 12, 2019.

Real-world effectiveness of anti-osteoporosis medications for the prevention of incident hip and clinical vertebral fractures in patients on long-term glucocorticoid therapy: A nationwide health insurance claims database study in Japan.

PURPOSE: Early initiation of anti-osteoporosis medications (AOMs) is recommended for patients on long-term glucocorticoid (GC) therapy. This study aimed to clarify the real-world effectiveness of AOMs against incident hip and vertebral fractures in patients undergoing GC therapy using the nationwide health insurance claims database of Japan (NDBJ). METHODS: Patients aged ≥50 years who were prescribed GC (≥5 mg/day prednisolone or equivalent) for ≥90 days and who were followed up regarding AOM prescription and hip and clinical vertebral fracture incidences for the subsequent 1080 days between 2012 and 2018 were selected from NDBJ. Associations of AOMs prescribed within 90 days since GC therapy initiation with hip or vertebral fracture risk were evaluated by Cox proportional hazards regression using propensity score inverse probability weighting (IPW) for receiving any AOM or individual AOMs. RESULTS: In total, 96,475 women and 98,385 men were included in the analysis; 38.0 % of women and 27.6 % of men received AOMs. Patients who received any AOM and those who received bisphosphonates or denosumab had a significantly lower risk of hip and clinical vertebral fractures than those who received no AOM in both sexes after propensity score IPW. Teriparatide was associated with an increased risk of both fractures in women and an increased risk of clinical vertebral fractures in men. Selection biases such as confounding by indication might have caused an underestimation of AOMs' protective effects. CONCLUSIONS: Bisphosphonates and denosumab were associated with a lower fracture incidence in patients on long-term GC therapy in real-world settings.