Incidence Of Nonvertebral Fractures Research Articles

Romosozumab in patients who experienced an on-study fracture: post hoc analyses of the FRAME and ARCH phase 3 trials.

Post hoc analysis evaluating efficacy and safety of romosozumab, administered in the immediate post‑fracture period, in the FRAME and ARCH phase 3 trials. In FRAME (NCT01575834) and ARCH (NCT01631214), postmenopausal women with osteoporosis were randomized 1:1 to romosozumab 210mg monthly or comparator (FRAME, placebo; ARCH, alendronate 70mg weekly) for 12months, followed by antiresorptive therapy (FRAME, denosumab; ARCH, alendronate). In patients who experienced on-study nonvertebral or new/worsening vertebral fracture by Month 12, we report the following: fracture and treatment‑emergent adverse event (TEAE) incidence through 36months, bone mineral density changes (BMD), and romosozumab timing. Due to the sample sizes employed, meaningful statistical comparisons between treatments were not possible. Incidence of on-study nonvertebral and vertebral fractures by Month 12 was numerically lower in romosozumab- versus comparator-treated patients (FRAME, 1.6% and 0.5% versus 2.1% and 1.6%; ARCH, 3.4% and 3.3% versus 4.6% and 4.9%, respectively). In those who experienced on-study nonvertebral fracture by Month 12, recurrent nonvertebral and subsequent vertebral fracture incidences were numerically lower in patients initially treated with romosozumab versus comparator (FRAME, 3.6% [2/56] and 1.8% [1/56] versus 9.2% [7/76] and 3.9% [3/76]; ARCH, 10.0% [7/70] and 5.7% [4/70] versus 12.6% [12/95] and 8.4% [8/95], respectively). Among those with on-study vertebral fracture by Month 12, recurrent vertebral and subsequent nonvertebral fracture incidences were numerically lower with romosozumab versus comparator (FRAME, 0.0% [0/17] and 0.0% [0/17] versus 11.9% [7/59] and 8.5% [5/59]; ARCH, 9.0% [6/67] and 7.5% [5/67] versus 15.0% [15/100] and 16.0% [16/100], respectively). In patients with fracture by Month12, no fracture‑related complications were reported in romosozumab-treated patients. BMD gains were numerically greater with romosozumab than comparators. Data suggest support for the efficacy and safety of continuing romosozumab treatment following fracture. NCT01575834; NCT01631214.

Cost-consequence analysis of continuous denosumab therapy for osteoporosis treatment in South Korea

BackgroundInsurance reimbursement provisions in South Korea limit osteoporosis medication availability for patients with T-scores exceeding − 2.5. This study aimed to evaluate the financial impact and fracture prevention of continuous denosumab therapy until a T-score>-2.0 (Dmab-C strategy), versus discontinuation of denosumab after reaching T-score>-2.5 (Dmab-D strategy) in osteoporosis patients.MethodsA cost-consequence analysis from a Korean healthcare system perspective was performed using a newly developed Markov model. The incidence of vertebral and non-vertebral fracture, fracture-related deaths, drug costs, and fracture-treatment costs were estimated and compared between Dmab-C and Dmab-D strategy over a lifetime in eligible patients aged 55 years.ResultsBase-case analysis revealed that Dmab-C prevented 32.21 vertebral fracture (VF) and 12.43 non-VF events per 100 patients over a lifetime, while reducing 1.29 fracture-related deaths. Lifetime direct healthcare cost saving per patient was KRW 1,354,655 if Dmab-C replaces Dmab-D. When productivity losses were considered, Dmab-C saved KRW 29,025,949 per patient compared to Dmab-D. The additional treatment costs of Dmab-C could be offset by the higher subsequent treatment costs and fracture treatment costs of Dmab-D. The sensitivity analysis showed consistent patterns with results of the base-case analysis.ConclusionContinuous treatment using denosumab until osteoporosis patients achieve and maintain a T-score of -2.0 would provide greater clinical and economic benefits in terms of fracture prevention and reduced mortality risks compared to outcomes from discontinuing treatment at a T-score of -2.5 or above. This new treatment strategy would effectively lower the risk of fractures and fracture-related mortality, ultimately leading to lower medical expenses.

Romosozumab Efficacy in Postmenopausal Women With No Prior Fracture Who Fulfill Criteria for Very High Fracture Risk

ObjectiveWe evaluated the efficacy of romosozumab in women from FRAME who had no prior fracture but met other criteria for very high fracture risk (VHFR). MethodsIn FRAME, postmenopausal women received romosozumab or placebo for 12 months (year 1) followed by denosumab for 12 months (year 2). In this post hoc analysis, we applied the following criteria from the American Association of Clinical Endocrinology to define VHFR: lumbar spine or total hip T-score <−3.0 and/or Fracture Risk Assessment Tool probability of major osteoporotic fracture >30% or hip fracture >4.5% to women with no fracture history at baseline (no fracture-VHFR [NF-VHFR]). Incidence of new vertebral, clinical, and nonvertebral fractures and mean bone mineral density (BMD) percentage change from baseline were assessed at years 1 and 2. ResultsOf the 7180 women in FRAME, 2825 were included in the NF-VHFR subgroup analysis. At year 1, romosozumab versus placebo reduced the incidence of new vertebral fracture (relative risk reduction [RRR]: 76%), clinical fracture (RRR: 60%), and nonvertebral fracture (RRR: 54%) (all P <.05). This fracture reduction was maintained through year 2 in women receiving the romosozumab-to-denosumab sequence versus the placebo-to-denosumab sequence for new vertebral, clinical, and nonvertebral fractures (RRR: 77%, 54%, and 46%, respectively; all P <.05). The mean BMD changes in both treatment groups were similar to those in the overall FRAME population at years 1 and 2. ConclusionRomosozumab significantly reduced vertebral, clinical, and nonvertebral fracture risk and increased the BMD more than placebo in women at VHFR.

Efficacy and safety of intravenous Zolidronic acid in the treatment of pediatric osteogenesis imperfecta: a systematic review.

Osteogenesis imperfecta is an inherited clinically heterogeneous disorder of bone metabolism characterized by bone and skeletal fragility and an increased risk of fractures. Pamidronate infusion was the standard treatment, but zoledronic acid is increasingly used to treat children with osteogenesis imperfecta. We conducted a systematic literature review to evaluate the efficacy and safety of intravenous zoledronic acid in the treatment of osteogenesis imperfecta in pediatric patients. A systematic review of the published literature was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Eligible articles were clinical trials and observational studies including pediatric patients (<16 years) with osteogenesis imperfecta treated with zoledronic acid. We selected articles published during the 20 past years. The selected languages were English and French. We included articles with a minimum sample size of five patients. Six articles fulfilled the selection criteria. The majority of patients were Chinese (58%). The predominant sex was male (65%), and the age of included patients ranged from 2.5 weeks to 16.8 years. For all patients, zoledronic infusions were administrated intravenously. The zoledronic treatment duration ranged from 1 to 3 years. Densitometry parameters before and after zoledronic treatment were evaluated and showed significant improvement both in lumbar spine-bone mineral density Z-score and femoral neck-bone mineral density Z-scores. A significant decrease in fracture rate has also been noted both in vertebral and nonvertebral fracture incidence. The two most common side effects were fever and flu-like reactions. None of the patients presented severe adverse events. Zoledronic acid appeared to be well-tolerated and effective in the treatment of pediatric osteogenesis imperfecta.

Denosumab treatment and infection risks in patients with osteoporosis: propensity score matching analysis of a national-wide population-based cohort study.

Denosumab demonstrates efficacy in reducing the incidence of hip, vertebral, and nonvertebral fractures in postmenopausal women with osteoporosis. We present a population-based national cohort study to evaluate the infection risks in patients with osteoporosis after long-term denosumab therapy. We used the Taiwan National Health Insurance Research Database (NHIRD) to identify patients with osteoporosis. The case cohort comprised patients treated with denosumab. Propensity score (PS) matching was used to select denosumab nonusers for the control cohort. The study period was between August 2011 and December 2017. Our study comprised 30,106 pairs of case and control patients. Patients receiving denosumab therapy had high risks of the following infections: pneumonia and influenza (adjusted hazard ratio [aHR]: 1.33; 95% confidence interval [CI]: 1.27 -1.39), urinary tract infection (aHR: 1.36; 95% CI:1.32 -1.40), tuberculosis (aHR: 1.60; 95% CI: 1.36 -1.87), fungal infection (aHR: 1.67; 95% CI:1.46 -1.90), candidiasis (aHR: 1.68; 95% CI: 1.47 -1.93), herpes zoster infection (aHR: 1.27; 95% CI: 1.19 -1.35), sepsis (aHR: 1.54; 95% CI:1.43 -1.66), and death (aHR: 1.26; 95% CI: 1.20 -1.32). However, the longer the duration of denosumab treatment, the lower the risk patients had of developing infections. Denosumab therapy is associated with a higher infection risk at the early periods of treatment. Nevertheless, the risk attenuates significantly after the 2nd year of therapy. Clinicians should closely monitor infection status in patients with osteoporosis during the initial stages of denosumab therapy.

Occurrence and relative risks for non-vertebral fractures in patients with ankylosing spondylitis compared with the general population: a register-based study from Sweden

ObjectivesTo estimate the incidence of non-vertebral fractures in ankylosing spondylitis (AS) compared with the general population.MethodsNationwide register-based cohort study including patients with AS (n=11 611, 65% men, mean age 48...

Association of Urinary Pentosidine Levels With the Risk of Fractures in Patients With Severe Osteoporosis: The Japanese Osteoporosis Intervention Trial-05 (JOINT-05).

ABSTRACTAssociations between urinary pentosidine, one of the advanced glycation end products in collagen, and the risk of fracture in patients with severe osteoporosis are unknown. In this study, we investigated whether the urinary pentosidine level is associated with the incidence of morphometric vertebral fracture and nonvertebral fracture using data of a randomized, controlled trial, JOINT‐05. JOINT‐05 enrolled Japanese women aged 75 years or older with primary osteoporosis. Patients were randomly assigned (1:1) to receive sequential therapy (teriparatide followed by alendronate) or monotherapy with alendronate for 120 weeks. Incidences of vertebral and nonvertebral fractures were assessed morphologically. During treatment, urinary levels of pentosidine and serum levels of bone turnover markers (osteocalcin, procollagen type I amino‐terminal propeptide, and tartrate‐resistant acid phosphatase 5b) were measured. A total of 967 patients with baseline pentosidine levels were included in the study. Of these, 137 had vertebral fractures, and 42 had nonvertebral fractures. The rate ratios for vertebral fracture for the second (30–39 pmol/mL), third (40–49 pmol/mL), and fourth quartile (≥50 pmol/mL) groups divided by pentosidine level compared with the first quartile (<30 pmol/mL) group were 1.65 (95% confidence interval [CI] 0.99–2.75, p = 0.06), 1.51 (95% CI 0.87–2.61, p = 0.14), and 1.69 (95% CI 1.01–2.83, p = 0.05), respectively. The corresponding rate ratios for nonvertebral fracture were 3.07 (95% CI 0.88–10.70, p = 0.08), 2.34 (95% CI 0.61–8.95, p = 0.22), and 3.95 (95% CI 1.14–13.67, p = 0.03), respectively. The association of the urinary pentosidine level with the incidence of nonvertebral fracture was the strongest among the biomarkers assessed in the study. In conclusion, the urinary pentosidine level was associated with the risk of fracture in patients with severe osteoporosis receiving teriparatide or alendronate. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

What is the impact of daily oral supplementation of vitamin D3 (cholecalciferol) plus calcium on the incidence of hip fracture in older people? A systematic review and meta-analysis.

Hip fractures have a huge impact in reducing the quality of life and increasing mortality. This review aims to assess the impact of daily oral supplementation of vitamin D3 plus calcium on the incidence of hip fracture in people over 65 years. PRISMA guidelines were followed and RCTs that evaluated the effectiveness of daily oral supplementation of vitamin D3 plus calcium in preventing hip fracture in adults over 65 years were included in the study. The databases such as Cochrane Library, Embase, Medline, PubMed, CINAHL, Web of Science and Scopus were searched from October 2019- January 2020.The Cochrane risk of bias tool was used to check the quality of the included studies. A meta-analysis with fixed effect model using Review Manager (Revman 5.3) was used to analyse the data. The meta-analysis of seven RCTs on vitamin D3 plus calcium supplementation and hip fracture (n= 12,620) identified odds ratio (OR) of 0.75; 95% Confidence interval (CI): 0.64, 0.87; p= .0003. Daily oral supplementation of 800 IU of Vitamin D3 plus 1200 mg of calcium was found more effective (n= 5676 participants; OR=0.69; 95% CI: 0.58, 0.82; p < .0001) than daily oral supplementation of 800 IU of Vitamin D3 plus 1000 mg of calcium (n= 6555,OR=1.08; 95% CI: 0.74, 1.56; p= .70) in reducing hip fracture. A meta-analysis of the seven RCTs to identify the incidence of non-vertebral fracture gave the OR of 0.80; 95% CI: 0.72, 0.89; p< .0001. A meta-analysis of three RCTs on femoral neck bone mineral density (BMD) (n= 483) gave a mean difference of 1.21; 95% CI: -0.79, 3.20; p= .24. Daily oral supplementation 800 IU of vitamin D3 plus 1200 mg of calcium reduces hip fracture and non-vertebral fracture in older people. Administering vitamin D3 and calcium supplements had no effect in increasing the femoral neck BMD. Even though it is evident from the review that optimal daily intake of vitamin D3 plus calcium supplementation help in the prevention of fracture, it is only one essential element in fracture prevention. Also, people who are on dietary supplements should be compliant with same for better result. Efforts to prevent bone loss and osteoporosis should begin from an early age. It includes maintaining a healthy lifestyle, optimal intake of calcium and vitamin D3, proper nutrition, adequate exposure to sunlight, exercise etc. Proper education on healthy lifestyle, avoiding risk factors like smoking, caffeine, alcohol and awareness of bone health should continue throughout life with emphasis during menopause when increased bone loss is expected.

The efficiency and safety of alendronate versus teriparatide for treatment glucocorticoid-induced osteoporosis: A meta-analysis and systematic review of randomized controlled trials.

Glucocorticoid-induced osteoporosis (GIOP) is the most common secondary osteoporosis, alendronate (ALE) and teriparatide (TPTD) are widely used in the treatment of GIOP. However, which of these two drugs has a better curative effect needs the support of evidence-based medicine. We searched PubMed, Embase, Cochrane Library, Web of Science, and Google Scholar for randomized controlled trials of ALE and TPTD in the treatment of glucocorticoid-induced osteoporosis until February 2022. These patients included in the study took glucocorticoid doses greater than 7.5 mg/d for more than 3 months before treatment with ALE and TPTD. The risk ratio (RR) and its 95% confidence interval (CI) are used as the influence index of discontinuous data, and the standardized mean difference (SMD) and its 95% CI are used as the influence index of continuous data. A total of 4102 patients were enrolled in all 5 studies that met the admission criteria. We found that compared with ALE, TPTD could reduce the rate of new vertebral fracture (RR = 0.13, 95% CI: 0.05-0.34, P<0.00001). TPTD increased LS bone mineral density (BMD) (0.53, 95% CI 0.42-0.64, P<0.00001), TH BMD (0.17, 95% CI 0.05-0.28, P = 0.004) and FN BMD (0.17, 95% CI 0.05-0.29, P = 0.006) compared to ALE. However, there was no significant difference in the incidence of non-vertebral fracture and adverse events between the two groups. Compared with ALE, TPTD is an effective drug to reduce vertebral fracture risk in patients with GIOP. Furthermore, long-term use of TPTD can increase the bone mineral density of LS, FN, and TH.

Comparative effectiveness and cardiovascular safety of abaloparatide and teriparatide in postmenopausal women new to anabolic therapy: A US administrative claims database study

Mini abstractReal-world evidence on the comparative effectiveness and safety of abaloparatide versus teriparatide in women with osteoporosis may help inform treatment decisions. Following 18 months of treatment, abaloparatide was comparable to teriparatide for prevention of nonvertebral fractures, resulted in a 22% risk reduction for hip fractures, and demonstrated similar cardiovascular safety.SummaryOsteoporotic fracture risk can be reduced with anabolic or antiresorptive medications. In addition to efficacy and safety data from controlled clinical trials, real-world evidence on comparative effectiveness and safety may help inform treatment decisions.IntroductionThe real-world effectiveness of abaloparatide versus teriparatide on nonvertebral fracture (NVF) incidence and cardiovascular safety during the 19-month period after treatment initiation were evaluated (NCT04974723).MethodsAnonymized US patient claims data from Symphony Health, Integrated Dataverse (IDV)®, May 1, 2017 to July 31, 2019, included women aged ≥ 50 years with ≥ 1 prescription of abaloparatide or teriparatide and no prior anabolic therapy. Most were enrolled in commercial and Medicare health plans. Index was the date of the initial prescription dispensed during the identification period. In 1:1 propensity score matched cohorts, time to first NVF following index date, major adverse cardiovascular events (MACE), and MACE + heart failure (HF) were compared between cohorts using a Cox proportional hazards model.ResultsPropensity score matching yielded 11,616 patients per cohort. Overall median age (interquartile range) was 67 (61, 75) years, and 25.6% had a fracture history. Over 19 months, 335 patients on abaloparatide and 375 on teriparatide had a NVF (hazard ratio [95% confidence interval]: 0.89 [0.77, 1.03]), and 121 and 154 patients, respectively, had a hip fracture [HR (95% CI): 0.78 (0.62, 1.00)]. The MACE and MACE + HF rates were similar between cohorts.ConclusionsFollowing 18 months of treatment, abaloparatide was comparable to teriparatide for prevention of NVF and similar cardiovascular safety was demonstrated between cohorts.

Clinical observations of osteoporosis in Japanese patients with rheumatoid arthritis.

Osteoporosis is one of the major adverse outcomes in patients with rheumatoid arthritis (RA). Recently, we and others have been reported many clinical observations related to osteoporosis in Japanese RA patients. In this article, I reviewed these findings. Japanese patients with RA have a 2-fold risk of fractures compared with those without RA. Among the fractures in Japanese RA patients, three-quarters of the fractures were non-vertebral fractures. The incidence of non-vertebral fractures did not change, despite an improvement in RA disease activity. Older age, female gender, history of fractures, history of total knee replacements, disease activity scores in 28 joints (DAS28), health assessment questionnaire disability index (HAQ-DI), low bone mineral density, glucocorticoid dose, and vitamin D deficiency were significantly associated with fractures. Older age, high body mass index (BMI), HAQ-DI, and polypharmacy were significantly associated with falls. BMI (both overweight and underweight), DAS28, and HAQ-DI were significantly associated with frailty. Half and three-quarters of Japanese men and women with RA had vitamin D deficiency, respectively. The incidence of osteonecrosis of the jaw may be higher in Japanese RA patients than in those without RA. Undertreatment of osteoporosis appears to exist in Japanese patients with RA.

A systematic review and meta-analysis of efficacy and safety of Romosozumab in postmenopausal osteoporosis.

The study was conducted to illustrate the effect of Romosozumab in postmenopausal osteoporosis patients. Romosozumab decreased the incidence of vertebral, nonvertebral, and clinical fractures significantly. In addition, decreased incidence of falls and increased bone mineral density at lumbar spine, total hip, and femoral neck was observed. Romosozumab is a monoclonal antibody that acts against the sclerostin pathway leading to enhanced bone formation and reduced bone resorption in patients with osteoporosis. Electronic search was performed on Medline (via PubMed), The Cochrane Central Register of Controlled Trials, and clinicaltrials.gov, till May 2020, for RCTs evaluating the effectiveness of Romosozumab in postmenopausal osteoporosis. RCTs evaluating the effect of Romosozumab on fractures and bone mineral density in postmenopausal osteoporosis patients. Meta-analysis was performed by Cochrane review manager 5 (RevMan) version 5.3. Cochrane risk of bias 2.0 tool and GRADE pro-GDT were applied for methodological quality and overall evidence quality, respectively. One hundred seventy-nine studies were screened, and 10 eligible studies were included in the analysis, with a total of 6137 patients in romosozumab group and 5732 patients in control group. Romosozumab significantly reduced the incidence of vertebral fractures [OR = 0.43 (95%CI = 0.35-0.52), High-quality evidence], nonvertebral fractures [OR = 0.78 (95%CI = 0.66-0.92), High quality], and clinical fractures [OR = 0.70 (95%CI = 0.60-0.82), High quality] at 24months. Significant reduction in incidence risk of falls [OR = 0.87 (95%CI = 0.78-0.96), High quality] was observed with romosozumab. Bone mineral density was significantly increased in the romosozumab treated groups at lumbar spine [MD = 12.66 (95%CI = 12.66-12.67), High quality], total hip [MD = 5.69 (95%CI = 5.68 - 5.69), Moderate quality], and femoral neck [MD = 5.18 (95%CI = 5.18-5.19), Moderate quality] at 12months. The total adverse events [RR = 0.98(95%CI = 0.96-1.01), Moderate quality] and serious adverse events [RR = 0.98(95%CI = 0.88-1.08), Moderate quality] with romosozumab were comparable to the control group. The current analysis with evidence on efficacy and safety of Romosozumab, authors opine to recommend the use of Romosozumab treatment for post-menopausal osteoporosis.Systematic review registration: PROSPERO registration number: CRD42019112196.

Retraction Note: Comparison of the effect of alendronate on lumbar bone mineral density and bone turnover in men and postmenopausal women with osteoporosis.

The purpose of the present study was to compare the effect of alendronate treatment on lumbar bone mineral density (BMD) and bone turnover in men and postmenopausal women with osteoporosis. Sixty men with primary or secondary osteoporosis and 318 women with postmenopausal osteoporosis were treated with alendronate. The primary end points were lumbar BMD and urinary cross-linked N-terminal telopeptides of type I collagen (NTX) and serum alkaline phosphatase (ALP) levels. The secondary end point was the incidence of vertebral and nonvertebral fractures. Forty-seven (78.3%) men and 254 (79.9%) women who could complete the 12-month trial were analyzed. The mean ages of men and postmenopausal women were 69.1 and 70.4 years, respectively. Both men and postmenopausal women showed higher levels of urinary NTX as compared with normal range of premenopausal women. Alendronate treatment decreased urinary NTX level by 39.2% in men and 45.4% in postmenopausal women at 3 months and serum ALP level by 17.8 and 21.0%, respectively, at 12 months. Following reduction in bone turnover markers, lumbar BMD increased 5.8 and 7.6% in men and postmenopausal women, respectively, at 12 months. Reduction in urinary NTX level and increase in lumbar BMD were smaller in men than in postmenopausal women. The incidence of vertebral and nonvertebral fractures was 10.6 and 8.5%, respectively, in men and 8.3 and 7.5%, respectively, in postmenopausal women, with no significant difference in these incidences between them. These results suggested that alendronate treatment effectively increased lumbar BMD from baseline in men with primary or secondary osteoporosis following reduction in bone turnover, although its efficacy did not appear to be greater than in postmenopausal women with osteoporosis.

Efficacy and safety of 18 anti-osteoporotic drugs in the treatment of patients with osteoporosis caused by glucocorticoid: A network meta-analysis of randomized controlled trials.

BackgroundGlucocorticoids are widely used in a variety of diseases, especially autoimmune diseases and inflammatory diseases, so the incidence of glucocorticoid-induced osteoporosis is high all over the world.ObjectivesThe purpose of this paper is to use the method of network meta-analysis (NMA) to compare the efficacy of anti-osteoporosis drugs directly and indirectly, and to explore the advantages of various anti-osteoporosis drugs based on the current evidence.MethodsWe searched PubMed, Embase and Cochrane Library for randomized controlled trials (RCTs), of glucocorticoid-induced osteoporosis (GIOP) and compared the efficacy and safety of these drugs by NMA. The risk ratio (RR) and its 95% confidence interval (CI) are used as the influence index of discontinuous data, and the standardized mean difference (SMD) and its 95% CI are used as the influence index of continuous data. The statistical heterogeneity was evaluated by the calculated estimated variance (τ2), and the efficacy and safety of drugs were ranked by the surface under the cumulative ranking curve (SUCRA). The main outcome of this study was the incidence of vertebral fracture after taking several different types of drugs, and the secondary results were the incidence of non-vertebral fracture and adverse events, mean percentage change of lumbar spine (LS) and total hip (TH)bone mineral density (BMD) from baseline to at least 12 months.ResultsAmong the different types of anti-GIOP, teriparatide (SUCRA 95.9%) has the lowest incidence of vertebral fracture; ibandronate (SUCRA 75.2%) has the lowest incidence of non-vertebral fracture; raloxifene (SUCRA 98.5%) has the best effect in increasing LS BMD; denosumab (SUCRA 99.7%) is the best in increasing TH BMD; calcitonin (SUCRA 92.4%) has the lowest incidence of serious adverse events.ConclusionsTeriparatide and ibandronate are effective drugs to reduce the risk of vertebral and non-vertebral fractures in patients with GIOP. In addition, long-term use of raloxifene and denosumab can increase the BMD of LS and TH.

Treatment of high fracture risk patients in routine clinical practice

This paper describes the various medical therapy regimens prescribed to osteoporotic patients with high fracture risk and the result of treatment. We carried out a retrospective cohort study in selected Osteoporosis Centers. Patients were considered to have high fracture risk in case of a history of a low-energy hip fracture or two or more vertebral or other site fractures. A total of 812 subjects (768 women and 44 men) aged 36-95years were included. The observation period was 2285.1 patient-years. Demographic data, clinical findings, and BMD data obtained by DXA, as well as a history of fractures that had occurred during the follow-up, were included in the analysis. Overall, at baseline, there were 637 non-vertebral fractures including 104 hip fractures. A total of 590 patients had vertebral fractures; of these, 69% suffered multiple fractures. Being on treatment, 119 (14.7%) patients developed new vertebral and non-vertebral fractures. The incidence of new non-vertebral fractures and hip fractures was 39.4 and 13.1 per 1000 patient-years. The total number of vertebral fractures increased by 24.8% from 1353 to 1689. The best results of the treatment were achieved in patients who were started on zoledronic acid, denosumab, or teriparatide and had an adequate duration of treatment. Although these patients had significantly lower BMD values at the time of diagnosis compared with other patients, they showed a lower incidence of new vertebral and hip fractures, during the follow-up. Therapy of patients at high risk of fractures started with more potent treatment regimens (zoledronic acid, denosumab and/or teriparatide) of adequate duration was more effective in terms of prevention of new vertebral and hip fractures as compared with other treatment options. However, treatment appears to be challenging given the number of recurrent fractures in patients on treatment and the frequency of drug withdrawal or replacement.

A 3-year postmarketing study on the safety and effectiveness of once-monthly risedronate in Japanese patients with osteoporosis

ObjectivesThis postmarketing study aims to evaluate the safety and effectiveness of oral administration of risedronate at 75 mg once monthly for 36 months in patients with osteoporosis in Japan. MethodsParticipants were ambulatory outpatients with osteoporosis who were ≥ 50 years old and had prevalent vertebral fractures. Outcomes were the incidence rate of adverse drug reaction (ADR), cumulative incidence of vertebral, nonvertebral, and hip fractures, the percent changes of lumbar spinal L2–4 bone mineral density (BMD), and low back pain. In addition, medication compliance was examined. ResultsSafety, vertebral fractures, and other outcomes were analyzed in 542, 328, and 535 patients, respectively. In the safety analysis set, 88.38% of the patients were women and the mean age was 75.9 years. The monthly medication compliance rate ranged from 83.24% to 95.38%. The incidence rate of ADRs, including 4 severe ADRs, was 10.52% (n = 57). The common ADRs were gastrointestinal disorders, musculoskeletal, and connective tissue disorders. No osteonecrosis of the jaw was reported. The cumulative incidences (95% CI) of vertebral, nonvertebral, and hip fractures at 36 months were 12.58% (8.61–18.18), 6.59% (4.31–10.01), and 1.58% (0.64–3.88), respectively. The L2–4 BMD increased by 10.59% compared with baseline value (P < 0.01), and the proportion of patients with low back pain decreased to 30.77%, at 36 months. ConclusionsAdministering 75 mg of risedronate once a month remains a favorable compliance rate and may be useful for the treatment of patients, even the elderly, with osteoporosis in daily practice.

Efficacy of once-weekly teriparatide in patients with glucocorticoid-induced osteoporosis: the TOWER-GO study.

Bisphosphonates are the standard treatment for glucocorticoid-induced osteoporosis (GIOP) with teriparatide being another option. While daily teriparatide has been shown to be effective in increasing bone mineral density (BMD), the efficacy of once-weekly teriparatide (56.5µg) has not yet been evaluated. The TOWER-GO study, a 72-week, multicenter, open-label, randomized controlled trial, was conducted in patients with GIOP to compare the effects of once-weekly teriparatide and once-weekly alendronate 35mg on BMD. Patients (N = 180) with GIOP for whom drug treatment was indicated according to the 2004 guidelines in Japan were randomized to receive once-weekly teriparatide (n = 89) or once-weekly alendronate (n = 91). The primary endpoint was the non-inferiority of percentage change in lumbar spine BMD at final follow-up. The secondary endpoints were the percentage change in BMD from baseline, incidence of bone fractures, and changes in bone turnover markers. While the non-inferiority of teriparatide to alendronate was not confirmed, BMD increased significantly from baseline with teriparatide and alendronate by 5.09% and 4.04%, respectively (both p < 0.05), at 72weeks. The incidence of vertebral and non-vertebral fractures was similar in both groups. Bone formation markers increased in the teriparatide group and decreased in the alendronate group. The non-inferiority of once-weekly teriparatide versus once-weekly alendronate in BMD change at 72weeks was not shown, but the increase in bone formation markers over time and the increase of BMD in GIOP patients treated with once-weekly teriparatide were confirmed.

Relationship between diffuse idiopathic skeletal hyperostosis and fragility vertebral fracture: a prospective study in older men.

To analyse the risk of incident vertebral and non-vertebral fracture in men with DISH. In 782 men ages 50-85 years, DISH was diagnosed using Resnick's criteria. In men followed prospectively for 7.5 years, a radiographic incident vertebral fracture was defined by a decrease of ≥20% or ≥4mm in any vertebral height vs baseline. Self-reported incident non-vertebral fractures were confirmed by medical records. Men with DISH had higher BMD at the lumbar spine (P < 0.05), but not at other skeletal sites. After adjustment for confounders including disc space narrowing (DSN) and endplate irregularity, the risk of vertebral fracture was higher in men with DISH vs men without DISH [10/164 (6.1%) vs 16/597 (2.7%), P < 0.05; odds ratio (OR) 2.89 (95% CI 1.15, 7.28), P < 0.05]. DISH and low spine BMD were each associated with a higher vertebral fracture risk. The vertebral fracture risk was higher in men who had both DISH and severe DSN. DISH and endplate irregularities (EIs) were each associated with higher vertebral fracture risk. DISH, DSN and EIs define the intervertebral space dysfunction, which was associated with higher vertebral fracture risk [OR 3.99 (95% CI 1.45, 10.98), P < 0.01]. Intervertebral space dysfunction improved the vertebral fracture prediction (ΔAUC = +0.111, P < 0.05), mainly in men with higher spine BMD (>0.9 g/cm2; ΔAUC = +0.189, P < 0.001). DISH was not associated with the risk of non-vertebral fracture. DISH is associated with higher vertebral fracture risk, independently of other risk factors. Assessment of the intervertebral space dysfunction components may improve the vertebral fracture prediction in older men.

Effect of Vitamin D Supplementation, Omega-3 Fatty Acid Supplementation, or a Strength-Training Exercise Program on Clinical Outcomes in Older Adults

The benefits of vitamin D, omega-3 fatty acids, and exercise in disease prevention remain unclear. To test whether vitamin D, omega-3s, and a strength-training exercise program, alone or in combination, improved 6 health outcomes among older adults. Double-blind, placebo-controlled, 2 × 2 × 2 factorial randomized clinical trial among 2157 adults aged 70 years or older who had no major health events in the 5 years prior to enrollment and had sufficient mobility and good cognitive status. Patients were recruited between December 2012 and November 2014, and final follow-up was in November 2017. Participants were randomized to 3 years of intervention in 1 of the following 8 groups: 2000 IU/d of vitamin D3, 1 g/d of omega-3s, and a strength-training exercise program (n = 264); vitamin D3 and omega-3s (n = 265); vitamin D3 and exercise (n = 275); vitamin D3 alone (n = 272); omega-3s and exercise (n = 275); omega-3s alone (n = 269); exercise alone (n = 267); or placebo (n = 270). The 6 primary outcomes were change in systolic and diastolic blood pressure (BP), Short Physical Performance Battery (SPPB), Montreal Cognitive Assessment (MoCA), and incidence rates (IRs) of nonvertebral fractures and infections over 3 years. Based on multiple comparisons of 6 primary end points, 99% confidence intervals are presented and P < .01 was required for statistical significance. Among 2157 randomized participants (mean age, 74.9 years; 61.7% women), 1900 (88%) completed the study. Median follow-up was 2.99 years. Overall, there were no statistically significant benefits of any intervention individually or in combination for the 6 end points at 3 years. For instance, the differences in mean change in systolic BP with vitamin D vs no vitamin D and with omega-3s vs no omega-3s were both -0.8 (99% CI, -2.1 to 0.5) mm Hg, with P < .13 and P < .11, respectively; the difference in mean change in diastolic BP with omega-3s vs no omega-3s was -0.5 (99% CI, -1.2 to 0.2) mm Hg; P = .06); and the difference in mean change in IR of infections with omega-3s vs no omega-3s was -0.13 (99% CI, -0.23 to -0.03), with an IR ratio of 0.89 (99% CI, 0.78-1.01; P = .02). No effects were found on the outcomes of SPPB, MoCA, and incidence of nonvertebral fractures). A total of 25 deaths were reported, with similar numbers in all treatment groups. Among adults without major comorbidities aged 70 years or older, treatment with vitamin D3, omega-3s, or a strength-training exercise program did not result in statistically significant differences in improvement in systolic or diastolic blood pressure, nonvertebral fractures, physical performance, infection rates, or cognitive function. These findings do not support the effectiveness of these 3 interventions for these clinical outcomes. ClinicalTrials.gov Identifier: NCT01745263.

Comparisons of different vitamin D supplementation for prevention of osteoporotic fractures: a Bayesian network meta-analysis and meta-regression of randomised controlled trials

Previous randomised controlled trials have shown the controversial effectiveness of oral vitamin D supplementation in preventing osteoporotic fractures. PubMed, EMBASE and Cochrane Library electronic databases were searched. Pairwise meta-analysis, Bayesian network meta-analysis and meta-regression were applied. A total of 33 studies containing 83,083 participants were included. Oral vitamin D supplementation showed no statistically significant on reducing the risk of total fractures (RR = 0.96, 95%CI = 0.87–1.05 p = 0.389). Vitamin D3 (700–800IU/d) plus calcium showed statistical significance in reducing the incidence of total, hip and non-vertebral fractures in the pairwise meta-analysis. Significant reductions were specifically identified in female in total and hip fractures. However, we did not observe any above significant results using Bayesian network meta-analyses. Strikingly, a meta-regression analysis identified an inverse association between the efficacy of fracture prevention and increased body mass index. Thus, we recommended that the vitamin D dose should be adjusted according to BMI based on further confirmation.