High-Impact Exercise Increased Femoral Neck Bone Density With No Adverse Effects on Imaging Markers of Knee Osteoarthritis in Postmenopausal Women

High-impact exercise can improve femoral neck bone mass but findings in postmenopausal women have been inconsistent and there may be concern at the effects of high-impact exercise on joint health. We investigated the effects of a high-impact exercise intervention on bone mineral density (BMD), bone mineral content (BMC), and section modulus (Z) as well as imaging biomarkers of osteoarthritis (OA) in healthy postmenopausal women. Forty-two women aged 55 to 70 years who were at least 12 months postmenopausal were recruited. The 6-month intervention consisted of progressive, unilateral, high-impact exercise incorporating multidirectional hops on one randomly assigned exercise leg (EL) for comparison with the contralateral control leg (CL). Dual-energy X-ray absorptiometry (DXA) was used to measure BMD, BMC, and Z of the femoral neck. Magnetic resonance imaging (MRI) of the knee joint was used to analyze the biochemical composition of articular cartilage using T2 relaxometry and to analyze joint pathology associated with OA using semiquantitative analysis. Thirty-five participants (61.7 ± 4.3 years) completed the intervention with a mean adherence of 76.8% ± 22.5%. Femoral neck BMD, BMC, and Z all increased in the EL (+0.81%, +0.69%, and +3.18%, respectively) compared to decreases in the CL (−0.57%, −0.71%, and −0.75%: all interaction effects p < 0.05). There was a significant increase in mean T2 relaxation times (main effect of time p = 0.011) but this did not differ between the EL and CL, indicating no global effect. Semiquantitative analysis showed high prevalence of bone marrow lesions (BML) and cartilage defects, especially in the patellofemoral joint (PFJ), with no indication that the intervention caused pathology progression. In conclusion, a high-impact exercise intervention that requires little time, cost, or specialist equipment improved femoral neck BMD with no negative effects on knee OA imaging biomarkers. Unilateral high-impact exercise is a feasible intervention to reduce hip fracture risk in healthy postmenopausal women. © 2019 American Society for Bone and Mineral Research.     

High‐Impact Mechanical Loading Increases Bone Material Strength in Postmenopausal Women—A 3‐Month Intervention Study

Bone adapts to loading in several ways, including redistributing bone mass and altered geometry and microarchitecture. Because of previous methodological limitations, it is not known how the bone material strength is affected by mechanical loading in humans. The aim of this study was to investigate the effect of a 3‐month unilateral high‐impact exercise program on bone material properties and microarchitecture in healthy postmenopausal women. A total of 20 healthy and inactive postmenopausal women (aged 55.6 ± 2.3 years [mean ± SD]) were included and asked to perform an exercise program of daily one‐legged jumps (with incremental number, from 3×10 to 4×20 jumps/d) during 3 months. All participants were asked to register their performed jumps in a structured daily diary. The participants chose one leg as the intervention leg and the other leg was used as control. The operators were blinded to the participant's choice of leg for intervention. The predefined primary outcome was change in bone material strength index (BMSi), measured at the mid tibia with a handheld reference probe indentation instrument (OsteoProbe). Bone microstructure, geometry, and density were measured with high‐resolution peripheral quantitative computed tomography (XtremeCT) at the ultradistal and at 14% of the tibia bone length (distal). Differences were analyzed by related samples Wilcoxon signed rank test. The overall compliance to the jumping program was 93.6%. Relative to the control leg, BMSi of the intervention leg increased 7% or 0.89 SD (p = 0.046), but no differences were found for any of the XtremeCT‐derived bone parameters. In conclusion, a unilateral high‐impact loading program increased BMSi in postmenopausal women rapidly without affecting bone microstructure, geometry, or density, indicating that intense mechanical loading has the ability to rapidly improve bone material properties before changes in bone mass or structure. © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.     

Effect of ONO‐5334 on Bone Mineral Density and Biochemical Markers of Bone Turnover in Postmenopausal Osteoporosis: 2‐Year Results From the OCEAN Study

Cathepsin K inhibitors, such as ONO‐5334, are being developed for the treatment of postmenopausal osteoporosis. However, their relative effects on bone resorption and formation, and how quickly the effects resolve after treatment cessation, are uncertain. The aim of this study was to examine the efficacy and safety of 24‐month treatment with ONO‐5334 and to assess the effect of treatment cessation over 2 months. We studied 197 postmenopausal women with osteoporosis or osteopenia with one fragility fracture. Patients were randomized to ONO‐5334 50 mg twice daily, 100 mg or 300 mg once daily, alendronate 70 mg once weekly (positive control), or placebo for 24 months. After 24 months, all ONO‐5334 doses were associated with increased bone mineral density (BMD) for lumbar spine, total hip, and femoral neck (p < 0.001). ONO‐5334 300 mg significantly suppressed the bone‐resorption markers urinary (u) NTX and serum and uCTX‐I throughout 24 months of treatment and to a similar extent as alendronate; other resorption marker levels remained similar to placebo (fDPD for ONO‐5334 300 mg qd) or were increased (ICTP, TRAP5b, all ONO‐5334 doses). Levels of B‐ALP and PINP were suppressed in all groups (including placebo) for approximately 6 months but then increased for ONO‐5334 to close to baseline levels by 12 to 24 months. On treatment cessation, there were increases above baseline in uCTX‐I, uNTX, and TRAP5b, and decreases in ICTP and fDPD. There were no clinically relevant safety concerns. Cathepsin K inhibition with ONO‐5334 resulted in decreases in most resorption markers over 2 years but did not decrease most bone formation markers. This was associated with an increase in BMD; the effect on biochemical markers was rapidly reversible on treatment cessation. © 2014 American Society for Bone and Mineral Research.     

A Comparison of Bone-Targeted Exercise With and Without Antiresorptive Bone Medication to Reduce Indices of Fracture Risk in Postmenopausal Women With Low Bone Mass: The MEDEX-OP Randomized Controlled Trial

The goal of the MEDEX-OP trial was to compare the efficacy of a known effective high-intensity resistance and impact training (HiRIT) with a low-intensity exercise control (Buff Bones® [BB]), alone or in combination with antiresorptive bone medication, on indices of fracture risk (bone mass, body composition, muscle strength, functional performance), compliance, and safety. Primary study outcomes were 8-month change in lumbar spine (LS) and total hip (TH) bone mineral density (BMD). Healthy postmenopausal women with low bone mass (T-score ≤ −1.0) on or off stable doses (≥12 months) of antiresorptive medication were recruited. A total of 115 women (aged 63.6 ± 0.7 years; body mass index [BMI] 25.5 kg/m²; femoral neck [FN] T-score −1.8 ± 0.1) were randomly allocated to 8-month, twice-weekly, 40-minute HiRIT (5 sets of 5 repetitions, >80% to 85% 1 repetition maximum) or BB (low-intensity, Pilates-based training), stratified by medication intake, resulting in four groups: HiRIT (n = 42), BB (n = 44), HiRIT-med (n = 15), BB-med (n = 14). HiRIT improved LS BMD (1.9 ± 0.3% versus 0.1 ± 0.4%, p < 0.001) and stature (0.2 ± 0.1 cm versus −0.0 ± 0.1 cm, p = 0.004) more than BB. Both programs improved functional performance, but HiRIT effects were larger for leg and back muscle strength and the five times sit-to-stand test (p < 0.05). There was a positive relationship between maximum weight lifted and changes in LS BMD and muscle strength in the HiRIT groups. Exploratory analyses suggest antiresorptive medication may enhance exercise efficacy at the proximal femur and lumbar spine. Exercise compliance was good (82.4 ± 1.3%) and both programs were well tolerated (7 adverse events: HiRIT 4; BB 3). HiRIT improved indices of fracture risk significantly more than Buff Bones®. More trials combining bone medication and bone-targeted exercise are needed. © 2021 American Society for Bone and Mineral Research (ASBMR).     

The Influence of High‐Impact Exercise on Cortical and Trabecular Bone Mineral Content and 3D Distribution Across the Proximal Femur in Older Men: A Randomized Controlled Unilateral Intervention

Regular exercisers have lower fracture risk, despite modest effects of exercise on bone mineral content (BMC). Exercise may produce localized cortical and trabecular bone changes that affect bone strength independently of BMC. We previously demonstrated that brief, daily unilateral hopping exercises increased femoral neck BMC in the exercise leg versus the control leg of older men. This study evaluated the effects of these exercises on cortical and trabecular bone and its 3D distribution across the proximal femur, using clinical CT. Fifty healthy men had pelvic CT scans before and after the exercise intervention. We used hip QCT analysis to quantify BMC in traditional regions of interest and estimate biomechanical variables. Cortical bone mapping localized cortical mass surface density and endocortical trabecular density changes across each proximal femur, which involved registration to a canonical proximal femur model. Following statistical parametric mapping, we visualized and quantified statistically significant changes of variables over time in both legs, and significant differences between legs. Thirty‐four men aged mean (SD) 70 (4) years exercised for 12‐months, attending 92% of prescribed sessions. In traditional regions of interest, cortical and trabecular BMC increased over time in both legs. Cortical BMC at the trochanter increased more in the exercise than control leg, whereas femoral neck buckling ratio declined more in the exercise than control leg. Across the entire proximal femur, cortical mass surface density increased significantly with exercise (2.7%; p < 0.001), with larger changes (> 6%) at anterior and posterior aspects of the femoral neck and anterior shaft. Endocortical trabecular density also increased (6.4%; p < 0.001), with localized changes of > 12% at the anterior femoral neck, trochanter, and inferior femoral head. Odd impact exercise increased cortical mass surface density and endocortical trabecular density, at regions that may be important to structural integrity. These exercise‐induced changes were localized rather than being evenly distributed across the proximal femur. © 2015 American Society for Bone and Mineral Research.     

Effects of a Targeted Multimodal Exercise Program Incorporating High‐Speed Power Training on Falls and Fracture Risk Factors in Older Adults: A Community‐Based Randomized Controlled Trial

Multimodal exercise programs incorporating traditional progressive resistance training (PRT), weight‐bearing impact training and/or balance training are recommended to reduce risk factors for falls and fracture. However, muscle power, or the ability to produce force rapidly, has emerged as a more crucial variable to functional decline than muscle strength or mass. The aim of this 12‐month community‐based randomized controlled trial, termed Osteo‐cise: Strong Bones for Life, was to evaluate the effectiveness and feasibility of a multimodal exercise program incorporating high‐velocity (HV)‐PRT, combined with an osteoporosis education and behavioral change program, on bone mineral density (BMD), body composition, muscle strength and functional muscle performance in older adults. Falls incidence was evaluated as a secondary outcome. A total of 162 older adults (mean ± SD; 67 ± 6 years) with risk factors for falls and/or low BMD were randomized to the Osteo‐cise program (n = 81) or a control group (n = 81). Exercise consisted of fitness center‐based HV‐PRT, weight‐bearing impact and challenging balance/mobility activities performed three times weekly. After 12 months, the Osteo‐cise program led to modest but significant net gains in femoral neck and lumbar spine BMD (1.0% to 1.1%, p < 0.05), muscle strength (10% to 13%, p < 0.05), functional muscle power (Timed Stair Climb, 5%, p < 0.05) and dynamic balance (Four Square Step Test 6%, p < 0.01; Sit‐to‐Stand, 16%, p < 0.001) relative to controls. There was no effect on total body lean mass or mobility (timed‐up‐and‐go), and no difference in falls rate (incidence rate ratio [IRR], 1.22; 95% confidence interval [CI], 0.72–2.04). In conclusion, this study demonstrates that the Osteo‐cise: Strong Bones for Life community‐based, multimodal exercise program represents an effective approach to improve multiple musculoskeletal and functional performance measures in older adults with risk factors for falls and/or low BMD. Although this did not translate into a reduction in the rate of falls, further large‐scale trials are needed to evaluate the efficacy of this multimodal approach on reducing falls and fracture. © 2014 American Society for Bone and Mineral Research.     

Effects of a Specialist‐Led,School Physical Education Program on Bone Mass,Structure, and Strength in Primary School Children: A 4‐Year Cluster Randomized Controlled Trial

This 4‐year cluster randomized controlled trial of 365 boys and 362 girls (mean age 8.1 ± 0.3 years) from grade 2 in 29 primary schools investigated the effects of a specialist‐taught physical education (PE) program on bone strength and body composition. All children received 150 min/week of common practice (CP) PE from general classroom teachers but in 13 schools 100 min/week of CP PE was replaced by specialized‐led PE (SPE) by teachers who emphasized more vigorous exercise/games combined with static and dynamic postural activities involving muscle strength. Outcome measures assessed in grades 2, 4, and 6 included: total body bone mineral content (BMC), lean mass (LM), and fat mass (FM) by DXA, and radius and tibia (4% and 66% sites) bone structure, volumetric density and strength, and muscle cross‐sectional area (CSA) by pQCT. After 4‐years, gains in total body BMC, FM, and muscle CSA were similar between the groups in both sexes, but girls in the SPE group experienced a greater gain in total body LM (mean 1.0 kg; 95% CI, 0.2 to 1.9 kg). Compared to CP, girls in the SPE group also had greater gains in cortical area (CoA) and cortical thickness (CoTh) at the mid‐tibia (CoA, 5.0% [95% CI, 0.2% to 1.9%]; CoTh, 7.5% [95% CI, 2.4% to 12.6%]) and mid‐radius (CoA, 9.3% [95% CI, 3.5% to 15.1%]; CoTh, 14.4% [95% CI, 6.1% to 22.7%]), whereas SPE boys had a 5.2% (95% CI, 0.4% to 10.0%) greater gain in mid‐tibia CoTh. These benefits were due to reduced endocortical expansion. There were no significant benefits of SPE on total bone area, cortical density or bone strength at the mid‐shaft sites, nor any appreciable effects at the distal skeletal sites. This study indicates that a specialist‐led school‐based PE program improves cortical bone structure, due to reduced endocortical expansion. This finding challenges the notion that periosteal apposition is the predominant response of bone to loading during the prepubertal and early‐pubertal period. © 2015 American Society for Bone and Mineral Research.     

Effect of Recent Spinal Cord Injury on Wnt Signaling Antagonists (Sclerostin and Dkk‐1) and Their Relationship With Bone Loss. A 12‐Month Prospective Study

Spinal cord injury (SCI) has been associated with a marked increase in bone loss and bone remodeling, especially short‐term after injury. The absence of mechanical load, mediated by osteocyte mechanosensory function, seems to be a causative factor related to bone loss in this condition. However, the pathogenesis and clinical management of this process remain unclear. Therefore, the aim of the study was to analyze the effect of recent SCI on the Wnt pathway antagonists, sclerostin and Dickkopf (Dkk‐1), and their relationship with bone turnover and bone mineral density (BMD) evolution. Forty‐two patients (aged 35 ± 14yrs) with a recent (<6months) complete SCI were prospectively included. Sclerostin and Dkk‐1, bone turnover markers (bone formation: PINP, bone ALP; resorption: sCTx) and BMD (lumbar spine, proximal femur, total body and lower extremities [DXA]) were assessed at baseline and at 6 and 12 months. The results were compared with a healthy control group. 22/42 patients completed the 12‐month follow‐up. At baseline, SCI patients showed a marked increase in bone markers (PINP and sCTx), remaining significantly increased at up to 6 months of follow‐up. Additionally, they presented significantly increased Dkk‐1 values throughout the study, whereas sclerostin values did not significantly change. BMD markedly decreased at the proximal femur (‐20.2 ± 5.4%, p < 0.01), total body (‐5.7 ± 2.2%, p = 0.02) and lower extremities (‐13.1 ± 4.5%, p = 0.01) at 12 months. Consequently, 59% of patients developed densitometric osteoporosis at 12 months. Patients with higher Dkk‐1 values (>58 pmol/L) at baseline showed higher sublesional BMD loss. In conclusion, this study shows that short‐term after SCI there is a marked increase in bone turnover and bone loss, the latter associated with an increase in Dkk‐1 serum levels. The persistence of increased levels of this Wnt antagonist throughout the study and their relationship with the magnitude of bone loss suggests a contributory role of this mediator in this process. © 2014 American Society for Bone and Mineral Research.     

Heterogeneous Spatial and Strength Adaptation of the Proximal Femur to Physical Activity: A Within-Subject Controlled Cross-Sectional Study

Physical activity (PA) enhances proximal femur bone mass, as assessed using projectional imaging techniques. However, these techniques average data over large volumes, obscuring spatially heterogeneous adaptations. The current study used quantitative computed tomography, statistical parameter mapping, and subject-specific finite element (FE) modeling to explore spatial adaptation of the proximal femur to PA. In particular, we were interested in adaptation occurring at the superior femoral neck and improving strength under loading from a fall onto the greater trochanter. High/long jump athletes (n = 16) and baseball pitchers (n = 16) were utilized as within-subject controlled models as they preferentially load their take-off leg and leg contralateral to their throwing arm, respectively. Controls (n = 15) were included but did not show any dominant-to-nondominant (D-to-ND) leg differences. Jumping athletes showed some D-to-ND leg differences but less than pitchers. Pitchers had 5.8% (95% confidence interval [CI] 3.9%–7.6%) D-to-ND leg differences in total hip volumetric bone mineral density (vBMD), with increased vBMD in the cortical compartment of the femoral neck and trochanteric cortical and trabecular compartments. Voxel-based morphometry analyses and cortical bone mapping showed pitchers had D-to-ND leg differences within the regions of the primary compressive trabeculae, inferior femoral neck, and greater trochanter but not the superior femoral neck. FE modeling revealed pitchers had 4.1% (95% CI 1.4%–6.7%) D-to-ND leg differences in ultimate strength under single-leg stance loading but no differences in ultimate strength to a fall onto the greater trochanter. These data indicate the asymmetrical loading associated with baseball pitching induces proximal femur adaptation in regions associated with weight bearing and muscle contractile forces and increases strength under single-leg stance loading. However, there were no benefits evident at the superior femoral neck and no measurable improvement in ultimate strength to common injurious loading during aging (ie, fall onto the greater trochanter), raising questions as to how to better target these variables with PA. © 2019 American Society for Bone and Mineral Research.     

Leisure‐Time Physical Activity and Risk of Fracture: A Cohort Study of 66,940 Men and Women

Physical activity has been associated with reduced risk of fracture, but it is not known how the intensity or frequency of physical activity influences this risk reduction. We aim to compare the risk of hip fracture and fracture of any locale between men and women with different levels of leisure‐time walking/bicycling and exercise. A total of 37,238 women (born 1914–1948) from the Swedish Mammography Cohort and 45,906 men (born 1918–1952) from the Cohort of Swedish Men were followed for a maximum of 17 years. Exposure and covariate information was collected through a self‐administered questionnaire in 1997. Incident fractures (5153 individuals with hip fracture and 15,043 with any type of fracture) and comorbidities were gathered from national and local patient registries. Hazard ratios (HRs) were calculated using Cox proportional hazards regression. Individuals who walked/bicycled less than 20 minutes per day had a lower rate of hip fracture (multivariable adjusted HR = 0.77; 95% confidence interval [CI] 0.70 to 0.85) and any fracture (HR = 0.87; 95% CI 0.82 to 0.92) compared with those who hardly ever walked/bicycled. These reduced rates were also evident in both sexes, in different age categories, for vertebral fractures and for non‐hip, non‐vertebral fractures. Those who reported exercise 1 hour per week had a lower rate of hip fracture (HR = 0.87; 95% CI 0.80 to 0.96) and any fracture (HR = 0.94; 95% CI 0.89 to 0.99) compared with those who exercised less than 1 hour per week. Only minor differences in HRs were observed in individuals with moderate compared with higher levels of walking/bicycling or exercise. Walking/bicycling and exercise showed almost equal reductions in rate of fracture when compared with those in a joint category with lowest activity. In conclusion, both moderate and high self‐reported frequency of physical activity is associated with reduced future risk of fracture. © 2017 American Society for Bone and Mineral Research.     

Effects of Loading Conditions on Articular Cartilage in a Metal‐on‐Cartilage Pairing

The aim of this in vitro study was to investigate the response of articular cartilage to frictional load when sliding against a metal implant, and identify potential mechanisms of damage to articular cartilage in a metal‐on‐cartilage pairing. Bovine osteochondral cylinders were reciprocally slid against metal cylinders (cobalt–chromium–molybdenum alloy) with several variations of load and sliding velocity using a microtribometer. The effects of different loads and velocities, and the resulting friction coefficients on articular cartilage, were evaluated by measuring histological and metabolic outcomes. Moreover, the biotribocorrosion of the metal was determined. Chondrocytes stimulated with high load and velocity showed increased metabolic activity and cartilage‐specific gene expression. In addition, higher load and velocity resulted in biotribocorrosion of the metal implant and damage to the surface of the articular cartilage, whereas low velocity and a high coefficient of friction increased the expression of catabolic genes. Articular cartilage showed particular responses to load and velocity when sliding against a metal implant. Moreover, metal implants showed tribocorrosion. Therefore, corrosion particles may play a role in the mechano‐biochemical wear of articular cartilage after implantation of a metal implant. These findings may be useful to surgeons performing resurfacing procedures and total knee arthroplasty. © 2019 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society J Orthop Res 37:2531–2539, 2019     

The Effects of Age,Adiposity, and Physical Activity on the Risk of Seven Site‐Specific Fractures in Postmenopausal Women

Risk factors for fracture of the neck of the femur are relatively well established, but those for fracture at other sites are little studied. In this large population study we explore the role of age, body mass index (BMI), and physical activity on the risk of fracture at seven sites in postmenopausal women. As part of the Million Women Study, 1,154,821 postmenopausal UK women with a mean age of 56.0 (SD 4.8) years provided health and lifestyle data at recruitment in 1996 to 2001. All participants were linked to National Health Service (NHS) hospital records for day‐case or overnight admissions with a mean follow‐up of 11 years per woman. Adjusted absolute and relative risks for seven site‐specific incident fractures were calculated using Cox regression models. During follow‐up, 4931 women had a fracture of the humerus; 2926 of the forearm; 15,883 of the wrist; 9887 of the neck of the femur; 1166 of the femur (not neck); 3199 a lower leg fracture; and 10,092 an ankle fracture. Age‐specific incidence rates increased gradually with age for fractures of forearm, lower leg, ankle, and femur (not neck), and steeply with age for fractures of neck of femur, wrist, and humerus. When compared to women with desirable BMI (20.0 to 24.9 kg/m²), higher BMI was associated with a reduced risk of fracture of the neck of femur, forearm, and wrist, but an increased risk of humerus, femur (not neck), lower leg, and ankle fractures (p < 0.001 for all). Strenuous activity was significantly associated with a decreased risk of fracture of the humerus and femur (both neck and remainder of femur) (p < 0.001), but was not significantly associated with lower leg, ankle, wrist, and forearm fractures. Postmenopausal women are at a high lifetime risk of fracture. BMI and physical activity are modifiable risk factors for fracture, but their associations with fracture risk differ substantially across fracture sites. © 2016 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research (ASBMR)     

Effect of Aerobic or Resistance Exercise,or Both,on Bone Mineral Density and Bone Metabolism in Obese Older Adults While Dieting: A Randomized Controlled Trial

Weight loss therapy of older adults with obesity is limited by weight loss–induced decrease in bone mineral density (BMD), which could exacerbate ongoing age-related bone loss and increase the risk for fractures. Therefore, it is recommended that weight loss therapy of older adults with obesity should include an intervention such as regular exercise to reduce the concomitant bone loss. However, the most appropriate exercise types to combine with weight loss therapy in this older population is unknown. In a randomized controlled trial, we performed a head-to-head comparison of aerobic or resistance exercise, or both, during matched ~10% weight loss in 160 older adults with obesity. We measured changes in BMD (total hip, femoral neck, trochanter, intertrochanter, one-third radius, lumbar spine) and bone markers. Changes between groups were analyzed using mixed-model repeated measures analyses of variance. After 6 months of intensive lifestyle interventions, BMD decreased less in the resistance group (−0.006 g/cm² [−0.7%]) and combination group (−0.012 g/cm² [−1.1%]) than in the aerobic group (−0.027 g/cm² [−2.6%]) (p = 0.001 for between-group comparisons). Serum C-telopeptide, procollagen type 1 N-propeptide, and osteocalcin concentrations increased more in the aerobic group (33%, 16%, and 16%, respectively) than in the resistance group (7%, 2%, and 0%, respectively) and combination group (11%, 2%, and 5%, respectively) (p = 0.004 to 0.048 for between-group comparisons). Multiple regression analyses revealed that the decline in whole body mass and serum leptin were the independent predictors of the decline in hip BMD (multiple R = 0.45 [p < .001]). These findings indicate that compared with aerobic exercise, resistance and combined aerobic and resistance exercise are associated with less weight loss–induced decrease in hip BMD and less weight loss–induced increase in bone turnover. Therefore, both resistance and combined aerobic and resistance exercise can be recommended to protect against bone loss during weight loss therapy of older adults with obesity. (LITOE ClinicalTrials.gov number NCT01065636.) © 2019 American Society for Bone and Mineral Research. Published 2019. This article is a U.S. Government work and is in the public domain in the USA.     

The Effect of an Exercise Intervention Program on Bone Health After Bariatric Surgery: A Randomized Controlled Trial

Exercise has been suggested as a therapeutic approach to attenuate bone loss induced by bariatric surgery (BS), but its effectiveness remains unclear. Our aim was to determine if an exercise-training program could induce benefits on bone mass after BS. Eighty-four patients, submitted to gastric bypass or sleeve gastrectomy, were randomized to either exercise (EG) or control group (CG). One month post-BS, EG underwent a 11-month supervised multicomponent exercise program, while CG received only standard medical care. Patients were assessed before BS and at 1, 6, and 12 months post-BS for body composition, areal bone mineral density (BMD), bone turnover markers, calciotropic hormones, sclerostin, bone material strength index, muscle strength, and daily physical activity. A primary analysis was conducted according to intention-to-treat principles and the primary outcome was the between-group difference on lumbar spine BMD at 12 months post-BS. A secondary analysis was also performed to analyze if the exercise effect depended on training attendance. Twelve months post-BS, primary analysis results revealed that EG had a higher BMD at lumbar spine (+0.024 g∙cm⁻² [95% confidence interval (CI) 0.004, 0.044]; p = .015) compared with CG. Among total hip, femoral neck, and 1/3 radius secondary outcomes, only 1/3 radius BMD improved in EG compared with CG (+0.013 g∙cm⁻² [95% CI 0.003, 0.023]; p = .020). No significant exercise effects were observed on bone biochemical markers or bone material strength index. EG also had a higher lean mass (+1.5 kg [95% CI 0.1, 2.9]; p = .037) and higher number of high impacts (+51.4 [95% CI 6.6, 96.1]; p = .026) compared with CG. In addition, secondary analysis results suggest that exercise-induced benefits may be obtained on femoral neck BMD but only on those participants with ≥50% exercise attendance compared with CG (+5.3% [95% CI 2.0, 8.6]; p = .006). Our findings suggest that an exercise program is an effective strategy to ameliorate bone health in post-BS patients. © 2020 American Society for Bone and Mineral Research (ASBMR).     

Effects of 24 Months of Treatment With Romosozumab Followed by 12 Months of Denosumab or Placebo in Postmenopausal Women With Low Bone Mineral Density: A Randomized,Double‐Blind,Phase 2, Parallel Group Study

Over 12 months, romosozumab increased bone formation and decreased bone resorption, resulting in increased bone mineral density (BMD) in postmenopausal women with low BMD (NCT00896532). Herein, we report the study extension evaluating 24 months of treatment with romosozumab, discontinuation of romosozumab, alendronate followed by romosozumab, and romosozumab followed by denosumab. Postmenopausal women aged 55 to 85 years with a lumbar spine (LS), total hip (TH), or femoral neck T‐score ≤–2.0 and ≥–3.5 were enrolled and randomly assigned to placebo, one of five romosozumab regimens (70 mg, 140 mg, 210 mg monthly [QM]; 140 mg Q3M; 210 mg Q3M) for 24 months, or open‐label alendronate for 12 months followed by romosozumab 140 mg QM for 12 months. Eligible participants were then rerandomized 1:1 within original treatment groups to placebo or denosumab 60 mg Q6M for an additional 12 months. Percentage change from baseline in BMD and bone turnover markers (BTMs) at months 24 and 36 and safety were evaluated. Of 364 participants initially randomized to romosozumab, placebo, or alendronate, 315 completed 24 months of treatment and 248 completed the extension. Romosozumab markedly increased LS and TH BMD through month 24, with largest gains observed with romosozumab 210 mg QM (LS = 15.1%; TH = 5.4%). Women receiving romosozumab who transitioned to denosumab continued to accrue BMD, whereas BMD returned toward pretreatment levels with placebo. With romosozumab 210 mg QM, bone formation marker P1NP initially increased after treatment initiation and gradually decreased to below baseline by month 12, remaining below baseline through month 24; bone resorption marker β‐CTX rapidly decreased after treatment, remaining below baseline through month 24. Transition to denosumab further decreased both BTMs, whereas after transition to placebo, P1NP returned to baseline and β‐CTX increased above baseline. Adverse events were balanced between treatment groups through month 36. These data suggest that treatment effects of romosozumab are reversible upon discontinuation and further augmented by denosumab. © 2018 The Authors Journal of Bone and Mineral Research published by Wiley Periodicals, Inc.