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Our results describe the rapid bone loss occurring after cessation of denosumab treatment. Further studies are needed to assess if patients have a higher risk of fracture after stopping DMAb and if so, which patients have the highest risk, and assess the role of transitioning to bisphosphonates in the long term.

SummaryRomosozumab is a therapy that stimulates bone formation and reduces bone resorption. In this study of postmenopausal women with low BMD, a second course of romosozumab following a period off treatment or on denosumab increased or maintained BMD, respectively, and was well tolerated, providing insight into treatment sequence options.IntroductionIn patients with high fracture risk, therapies that stimulate bone formation provide rapid BMD gains; currently available agents, parathyroid hormone receptor agonists, are limited to a 2-year lifetime exposure and generally used for a single treatment course. However, for long-term osteoporosis management, a second treatment course may be appropriate. Romosozumab, a therapy with the dual effect of increasing bone formation and decreasing bone resorption, reduces fracture risk within 12 months. Here, we report efficacy and safety of a second romosozumab course.MethodsIn this phase 2, dose-finding study, postmenopausal women with low bone mass (T-score ≤ − 2.0 and ≥ − 3.5) received romosozumab or placebo (month 0–24) followed by placebo or denosumab (month 24–36); participants then received a year of romosozumab (month 36–48).ResultsOf 167 participants who entered the month 36–48 period, 35 had been initially randomized to romosozumab 210 mg monthly. In participants who received romosozumab 210 mg monthly followed by placebo, a second romosozumab course (n = 19) increased BMD by amounts similar to their initial treatment (month 0–12) at the lumbar spine (12.4%; 12.0%, respectively) and total hip (6.0%; 5.5%, respectively). Following denosumab, a second romosozumab course (n = 16) increased BMD at the lumbar spine (2.3%) and maintained BMD at the total hip. Safety profiles were similar between first and second romosozumab courses.ConclusionsAfter 12 months off-treatment, a second romosozumab course again led to rapid and large BMD gains. Following denosumab, BMD gains with romosozumab were smaller than with initial treatment. No new safety findings were observed during the second course.Electronic supplementary materialThe online version of this article (10.1007/s00198-019-05146-9) contains supplementary material, which is available to authorized users.

We have recently identified a significant deterioration of bone microarchitecture in premenopausal women with newly diagnosed celiac disease (CD) using high-resolution peripheral quantitative computed tomography (HRpQCT). The aim of this work was to assess changes in bone microarchitecture after 1 year on a gluten-free diet (GFD) in a cohort of premenopausal women. We prospectively enrolled 31 consecutive females at diagnosis of CD; 26 of them were reassessed 1 year after GFD. They all underwent HRpQCT scans of distal radius and tibia, areal BMD by DXA, and biochemical tests (bone-specific parameters and CD serology) at both time points. Secondary, we compared 1-year results with those of a control group of healthy premenopausal women of similar age and BMI in order to assess whether the microarchitectural parameters of treated CD patients had reached the values expected for their age. Most parameters continued to be significantly lower than those of healthy controls. This prospective HRpQCT study showed that most trabecular parameters altered at CD diagnosis improved significantly by specific treatment (GFD) and calcium and vitamin D supplementation. However, there were still significant differences with a control group of women of similar age and BMI. In the prospective follow-up of this group of patients we expect to be able to assess whether bone microarchitecture attains levels expected for their age.

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The Active‐Controlled Fracture Study in Postmenopausal Women With Osteoporosis at High Risk (ARCH) trial (NCT01631214; https://clinicaltrials.gov/ct2/show/NCT01631214) showed that romosozumab for 1 year followed by alendronate led to larger areal bone mineral density (aBMD) gains and superior fracture risk reduction versus alendronate alone. aBMD correlates with bone strength but does not capture all determinants of bone strength that might be differentially affected by various osteoporosis therapeutic agents. We therefore used quantitative computed tomography (QCT) and finite element analysis (FEA) to assess changes in lumbar spine volumetric bone mineral density (vBMD), bone volume, bone mineral content (BMC), and bone strength with romosozumab versus alendronate in a subset of ARCH patients. In ARCH, 4093 postmenopausal women with severe osteoporosis received monthly romosozumab 210 mg sc or weekly oral alendronate 70 mg for 12 months, followed by open‐label weekly oral alendronate 70 mg for ≥12 months. Of these, 90 (49 romosozumab, 41 alendronate) enrolled in the QCT/FEA imaging substudy. QCT scans at baseline and at months 6, 12, and 24 were assessed to determine changes in integral (total), cortical, and trabecular lumbar spine vBMD and corresponding bone strength by FEA. Additional outcomes assessed include changes in aBMD, bone volume, and BMC. Romosozumab caused greater gains in lumbar spine integral, cortical, and trabecular vBMD and BMC than alendronate at months 6 and 12, with the greater gains maintained upon transition to alendronate through month 24. These improvements were accompanied by significantly greater increases in FEA bone strength (p < 0.001 at all time points). Most newly formed bone was accrued in the cortical compartment, with romosozumab showing larger absolute BMC gains than alendronate (p < 0.001 at all time points). In conclusion, romosozumab significantly improved bone mass and bone strength parameters at the lumbar spine compared with alendronate. These results are consistent with greater vertebral fracture risk reduction observed with romosozumab versus alendronate in ARCH and provide insights into structural determinants of this differential treatment effect. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Denosumab is the first fully human monoclonal antibody that inhibits the formation, function, and survival of osteoclasts by blocking the interaction of receptor activator of nuclear factor-κB (RANK) ligand with its osteoclastic receptor RANK. Clinical studies have shown that the decreased bone resorption and increased bone mineral density resulting from the use of denosumab 60 mg twice yearly entail significant risk reduction of vertebral, hip, and nonvertebral fractures in women with postmenopausal osteoporosis, with an acceptable rate of side effects so far. Following its approval by the US Food and Drug Administration and the European Medicines Agency, a number of clinical trials with denosumab are ongoing to demonstrate its value for other indications and to further characterize its effects on immunomodulation. Denosumab offers a new choice for the treatment of postmenopausal osteoporosis in patients at high risk for fracture.

The aim of this study was to present the results of the triennial SBAM regional program aimed at monitoring 8-year old children in the Apulian region of Southern Italy from 2013 to 2016. The program included at launch 17,102 children in the first year, 16,104 children in the second year and 14,847 children in the third year. The sample who completed the monitoring was less than the number of children recruited for organizational and didactic reasons (N = 15,231, N = 14,147 and N = 13,362). SBAM was a multi-component program and included different integrated action plans: physical education, active transport (pedibus), and methods for developing healthy eating habits. For each year, four motor tests (long jump standing, shuttle run, 6 min walk test, and medicine ball throw), a motor coordination test and two self-reports for evaluating self-efficacy and enjoyment were proposed to all children. The results showed gender and group differences (normal-weight vs. overweight-obese) in both motor tests and self-reports (p < 0.05). The annual results of the motor tests were sorted in deciles in order to have a regional observation and monitoring database concerning the motor development skills among children and preadolescents. Boys showed motor performance, perceived self-efficacy scores and enjoyment higher than females in three years. Growth influences the development of motor abilities; overweight and obese males and females showed a different development of motor performance that was lower than in children with a BMI in the norm. It is necessary to develop physical education in primary school, increasing opportunities and adapting them to the needs of all children. SBAM project highlighted the need to promote interdisciplinary and inter-institutional actions to promote child health and acquire physically active lifestyles.