Effect on bone turnover markers of once-yearly intravenous infusion of zoledronic acid versus daily oral risedronate in patients treated with glucocorticoids

Objective. Long-term glucocorticoid use is accompanied by rapid bone loss; however, early treatment with bisphosphonates prevents bone loss and reduces fracture risk. The aim of this study was to examine the effects of two bisphosphonates, i.v. zoledronic acid (ZOL) versus oral risedronate (RIS), on bone turnover markers (BTMs) in subjects with glucocorticoid-induced osteoporosis (GIO). Methods. Patients were randomly stratified according to the duration of pre-study glucocorticoid therapy [prevention subpopulation (ZOL, n = 144; RIS, n = 144) ≤3 months, treatment subpopulation (ZOL, n = 272; RIS, n = 273) >3 months]. Changes in β-C-terminal telopeptides of type 1 collagen (β-CTx), N-terminal telopeptide of type I collagen (NTx), procollagen type 1 N-terminal propeptide (P1NP) and bone-specific alkaline phosphatase (BSAP) from baseline were measured on day 10 and months 3, 6 and 12. Results. At most time points, there were significantly greater reductions (P < 0.05) in the concentrations of serum β-CTx, P1NP and BSAP and urine NTx in subjects on ZOL compared with RIS in both males and females of the treatment and prevention subpopulations. In pre- and post-menopausal women, there were significantly greater reductions in the concentrations of BTMs with ZOL compared with RIS. At 12 months, ZOL had significantly greater reductions compared with RIS (P < 0.05) for β-CTx, P1NP, BSAP and NTx levels, independent of glucocorticoid dose. Conclusions. Once-yearly i.v. infusion of ZOL 5 mg was well tolerated in different subgroups of GIO patients. ZOL was non-inferior to RIS and even superior to RIS in the response of BTMs in GIO patients. Trial registration: ClinicalTrials.gov, http://clinicaltrials.gov, NCT0010062

A meta-analysis of previous falls and subsequent fracture risk in cohort studies

NC Harvey acknowledges funding from the UK Medical Research Council (MC_PC_21003; MC_PC_21001). The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through 75N92021D00001, 75N92021D00002, 75N92021D00003, 75N92021D00004, and 75N92021D00005. Funding for the MrOS USA study comes from the National Institute on Aging (NIA), the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Center for Advancing Translational Sciences (NCATS), and NIH Roadmap for Medical Research under the following grant numbers: U01 AG027810, U01 AG042124, U01 AG042139, U01 AG042140, U01 AG042143, U01 AG042145, U01 AG042168, U01 AR066160, and UL1 TR000128. Funding for the SOF study comes from the National Institute on Aging (NIA), and the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), supported by grants (AG05407, AR35582, AG05394, AR35584, and AR35583). Funding for the Health ABC study was from the Intramural research program at the National Institute on Aging under the following contract numbers: NO1-AG-6–2101, NO1-AG-6–2103, and NO1-AG-6–2106.Peer reviewedPostprin

Pregnancy- and lactation-induced osteoporosis: a social-media-based survey

Abstract Background Pregnancy- and lactation-induced osteoporosis (PLO) presenting as spinal fractures is rare, and the spectrum of clinical presentation, risk factors and pathophysiology are incompletely understood. The aim of this study was to delineate clinical parameters, risk factors and osteoporosis-related quality of life (QOL) of women with PLO. Methods Participants of a social-media (WhatsApp) PLO group and mothers of a parents’ WhatsApp group (control group) were offered to fill a questionnaire, including an osteoporosis-related QOL section. The groups were compared using the independent Students t test for numerical variables, and the Chi-square test or Fisher’s exact test for categorical variables. Results Twenty-seven women with PLO and 43 in the control group (aged 36.2 ± 4.7 and 38.8 ± 4.3 years, respectively, p = 0.04) participated. Among women with PLO, more than 5 vertebrae were involved in 13 (48%), 4 vertebrae in 6 (22%), and 3 or fewer vertebrae in 8 (30%). Among the 24 women with relevant data, 21 (88%) had nontraumatic fractures; 3 (13%) women had fractures during pregnancy, and the remaining during the early postpartum period. Diagnosis was delayed for over 16 weeks for 11 (41%) women; 16 (67%) received teriparatide. Significantly lower proportions of women in the PLO group engaged in physical activity over 2 hours/week, before and during pregnancy (37 vs. 67%, p < 0.015 and 11 vs. 44%, p < 0.003, respectively). A lower proportion of the PLO than the control group reported calcium supplementation during pregnancy (7% vs. 30%, p = 0.03) and a higher proportion reported treatment with low-molecular-weight-heparin during pregnancy (p = 0.03). Eighteen (67%) of the PLO group expressed fear of fractures and 15 (56%) fear of falls, compared to none and 2%, respectively, of the control group (p < 0.00001 for both). Conclusions Most of the women with PLO who responded to our survey reported spinal fractures involving multiple vertebrae, delayed diagnosis, and treatment with teriparatide. Compared to a control group, they reported less physical activity and impaired QOL. For this uncommon yet severe condition, a multidisciplinary effort should be exerted for early identification and treatment, to alleviate back pain, prevent subsequent fractures and improve QOL

Bisphosphonates Use and Risk of Hip Fractures

Background: Osteoporosis affects 200 million women worldwide, and fractures resulting from bone fragility are a major complication. Bisphosphonates slow down bone resorption by osteoclasts and have been shown to lower the risk of hip fractures among patients with osteoporosis in clinical trial settings. Most clinical guidelines recommend pharmacological treatment for postmenopausal women with an existing fracture or bone density T-score of -2.5 or lower. These guidelines were based on randomized controlled trials that typically lasted 3–4 years, although some of these studies have been extended for up to 10 years. We undertook this study to examine the association between adherence with bisphosphonate therapy and long-term risk of hip fracture, using up to 14 years of retrospective observation. Methods: Included in the present nested case-control study were osteoporotic women (N = 14,357) who initiated bisphosphonate therapy between the years 2000 and 2010 and were retrospectively followed for incident hip fracture through November 2014. All cases of primary hip fracture within the cohort (n = 411) were individually matched with 411 controls based on age (± 1 year) and calendar year at therapy initiation as well as follow-up duration (± 1 year). For each study participant, the total dispensed packs of bisphosphonates during the follow-up period were counted. Results: Compared to patients discontinuing therapy within 1 month, therapy with bisphosphonates for 1 to 3 years and 3 to 6 years was associated with adjusted odds ratios (and 95% confidence intervals) for hip fractures of 0.48 (0.27–0.86) and 0.40 (0.22–0.73), respectively. Comparable odds ratios were calculated for patients covered for longer periods –– 0.36 (0.17–0.76) for 6 to 8 years, and 0.57 (0.27–1.21) for 8 years or more. Conclusion: Results suggest that 3 years or more of bisphosphonates use is associated with a substantially lower risk of primary hip fracture compared to nonpersistent patients. The results do not indicate further reduction in risk among patients treated for 8 years or more

Study description and baseline characteristics of the population enrolled in a multinational, observational study of teriparatide in postmenopausal women with osteoporosis: the Asia and Latin America Fracture Observational Study (ALAFOS)

Objective: To describe the study design and baseline patient characteristics of the Asia and Latin America Fracture Observational Study (ALAFOS) to better understand the profile of patients receiving teriparatide during the course of routine clinical practice in Asia, Latin America, the Middle East and Russia. Methods: Prospective, observational, non-interventional study in postmenopausal women with osteoporosis who are prescribed teriparatide for up to 24 months, according to local medical standards, with a 12 month post-treatment follow-up. Measures: Demographics, risk factors for osteoporosis and fractures, history of fracture, prior osteoporosis medications, comorbidities, physical function, back pain and quality of life (QoL). Results: In total 3031 postmenopausal women (mean age 72.5 years) recruited at 152 sites in 20 countries were analyzed; 62.9% had a history of fragility fracture after age 40 (33.0% of patients with spinal, 14.2% with hip fractures). The mean (SD) bone mineral density T-scores at baseline were -3.06 (1.40) and -2.60 (1.05) at the lumbar spine and femoral neck, respectively. At entry, 43.7% of patients were naive to prior osteoporosis treatments; 40.5% of patients reported >= 1 fall in the past year. The median (Q1; Q3) EuroQoL Visual Analog Scale (EQ-VAS) for perceived overall health status was 60 (50; 80). The mean (SD) worst back pain Numeric Rating Scale in the last 24 hours was 4.6 (3.3). Conclusions: Our data indicates that patients who were prescribed teriparatide in the ALAFOS participant countries had severe osteoporosis, high prevalence of fractures, disabling back pain and poor QoL. The frequency of patients receiving prior osteoporosis medications was lower than in previous observational studies conducted in other locations.Eli Lilly B3D-MC-B02