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Bone marrow adipose tissue (BMAT) has been postulated to mediate skeletal fragility in type 2 diabetes (T2D) and obesity. Roux‐en‐Y gastric bypass (RYGB) induces a substantial weight loss and resolution of comorbidities. However, the procedure induces increased bone turnover and fracture rates. No previous study has evaluated biopsy‐measured BMAT fraction preoperatively and after RYGB. In this study, we aimed to investigate BMAT fraction of the hip in participants with and without T2D preoperatively and 1 year after RYGB and explore factors associated with BMAT change. Patients with morbid obesity scheduled for RYGB were examined preoperatively and 1 year after RYGB. Forty‐four participants were included and preoperative examinations were possible in 35. Of these, 33 (94%) met for follow‐up, 2 were excluded, and BMAT estimation was not possible in 1. Eighteen (60%) of the participants were females and 11 (37%) had T2D. Preoperative BMAT fraction was positively associated with glycosylated hemoglobin and negatively associated with areal bone mineral density (aBMD). After RYGB, BMAT fraction decreased from 40.4 ± 1.7% to 35.6 ± 12.8%, p = 0.042, or with mean percent change of 10.7% of preoperative BMAT fraction. Change in BMAT fraction was positively associated with change in body mass index (BMI) and total body fat. In females, we observed a mean percent reduction of 22.4 ± 19.6%, whereas in males BMAT increased with a mean percent of 6.8 ± 37.5%, p = 0.009. For males, changes in estradiol were associated with BMAT change; this was not observed for females. In participants with and without T2D, the mean percent BMAT reduction was 5.8 ± 36.9% and 13.5 ± 28.0%, respectively, p = 0.52. We conclude that a high BMAT seems to be associated with lower aBMD and poorer glycemic control in obese subjects. After RYGB, we observed a significant decrease in BMAT. The reduction in BMAT did not differ between participants with and without T2D, but appeared sex specific. © 2019 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Clinical data suggest concomitant therapy with bisphosphonates and parathyroid hormone (PTH) may blunt the anabolic effect of PTH; rodent models suggest that infrequently administered bisphosphonates may interact differently. To evaluate the effects of combination therapy with an intravenous infusion of zoledronic acid 5 mg and daily subcutaneous recombinant human (rh)PTH(1-34) (teriparatide) 20 µg versus either agent alone on bone mineral density (BMD) and bone turnover markers, we conducted a 1-year multicenter, multinational, randomized, partial double-blinded, controlled trial. 412 postmenopausal women with osteoporosis (mean age 65 ± 9 years) were randomized to a single infusion of zoledronic acid 5 mg plus daily subcutaneous teriparatide 20 µg ( n = 137), zoledronic acid alone ( n = 137), or teriparatide alone ( n = 138). The primary endpoint was percentage increase in lumbar spine BMD (assessed by dual-energy X-ray absorptiometry [DXA]) at 52 weeks versus baseline. Secondary endpoints included change in BMD at the spine at earlier time points and at the total hip, trochanter, and femoral neck at all time points. At week 52, lumbar spine BMD had increased 7.5%, 7.0%, and 4.4% in the combination, teriparatide, and zoledronic acid groups, respectively ( p < .001 for combination and teriparatide versus zoledronic acid). In the combination group, spine BMD increased more rapidly than with either agent alone ( p < .001 versus both teriparatide and zoledronic acid at 13 and 26 weeks). Combination therapy increased total-hip BMD more than teriparatide alone at all times (all p < .01) and more than zoledronic acid at 13 weeks ( p < .05), with final 52-week increments of 2.3%, 1.1%, and 2.2% in the combination, teriparatide, and zoledronic acid groups, respectively. With combination therapy, bone formation (assessed by serum N-terminal propeptide of type I collagen [PINP]) increased from 0 to 4 weeks, declined minimally from 4 to 8 weeks, and then rose throughout the trial, with levels above baseline from 6 to 12 months. Bone resorption (assessed by serum β-C-telopeptide of type I collagen [β-CTX]) was markedly reduced with combination therapy from 0 to 8 weeks (a reduction of similar magnitude to that seen with zoledronic acid alone), followed by a gradual increase after week 8, with levels remaining above baseline for the latter half of the year. Levels for both markers were significantly lower with combination therapy versus teriparatide alone ( p < .002). Limitations of the study included its short duration, lack of endpoints beyond DXA-based BMD (e.g., quantitative computed tomography and finite-element modeling for bone strength), lack of teriparatide placebo, and insufficient power for fracture outcomes. We conclude that while teriparatide increases spine BMD more than zoledronic acid and zoledronic acid increases hip BMD more than teriparatide, combination therapy provides the largest, most rapid increments when both spine and hip sites are considered. © 2011 American Society for Bone and Mineral Research. [ABSTRACT FROM AUTHOR]

The article discusses a study about the antifracture efficacy of zoledronic acid in relation to the timing of the administration of its first dose following hip fracture. It describes zoledronic acid as a potent biphosphonate which can prevent bone turnover markers as well as increase body mass index (BMD) when administered intravenously once a year. The study involved patients aged 50 years and above who were administered with the drug within 90 days after undergoing surgery for low-trauma hip fracture.

The article presents the study that investigates the close association between bone and vasculature which play a vital role in the regulation of bone remodeling and fracture repair. The researchers found a decrease in bone turnover that lead to a decrease in surfaces covered with remodeling compartments. The reduction of bone remodeling compartment space brought about by antiresorptive therapies reduce the number of skeletal events in advanced cancer.

The author offers information on slerostin deficiency and its association with altered bone composition. He mention three variables responsible for bone strength such as bone mass, distribution of mass and bone material properties, discusses relation of sclerosteosis and van Buchem disease to mutations of the SOST gene, the gene responsible for producing sclerostin and mentions the study of bone material properties of bone formed during sclerostin inhibition by author N. Hassler and others.