Changes in vertebral bone marrow fat and bone mass after gastric bypass surgery: A pilot study.

Bone marrow fat may serve a metabolic role distinct from other fat depots, and it may be altered by metabolic conditions including diabetes. Caloric restriction paradoxically increases marrow fat in mice, and women with anorexia nervosa have high marrow fat. The longitudinal effect of weight loss on marrow fat in humans is unknown. We hypothesized that marrow fat increases after Roux-en-Y gastric bypass (RYGB) surgery, as total body fat decreases. In a pilot study of 11 morbidly obese women (6 diabetic, 5 nondiabetic), we measured vertebral marrow fat content (percentage fat fraction) before and 6 months after RYGB using magnetic resonance spectroscopy. Total body fat mass declined in all participants (mean ± SD decline 19.1 ± 6.1 kg or 36.5% ± 10.9%, p<0.001). Areal bone mineral density (BMD) decreased by 5.2% ± 3.5% and 4.1% ± 2.6% at the femoral neck and total hip, respectively, and volumetric BMD decreased at the spine by 7.4% ± 2.8% (p<0.001 for all). Effects of RYGB on marrow fat differed by diabetes status (adjusted p=0.04). There was little mean change in marrow fat in nondiabetic women (mean +0.9%, 95% CI -10.0 to +11.7%, p=0.84). In contrast, marrow fat decreased in diabetic women (-7.5%, 95% CI -15.2 to +0.1%, p=0.05). Changes in total body fat mass and marrow fat were inversely correlated among nondiabetic (r=-0.96, p=0.01) but not diabetic (r=0.52, p=0.29) participants. In conclusion, among those without diabetes, marrow fat is maintained on average after RYGB, despite dramatic declines in overall fat mass. Among those with diabetes, RYGB may reduce marrow fat. Thus, future studies of marrow fat should take diabetes status into account. Marrow fat may have unique metabolic behavior compared with other fat depots.

Serum 25-hydroxyvitamin D concentration does not independently predict incident diabetes in older women.

AIMS: To investigate whether 25-hydroxyvitamin D concentration was associated with incident diabetes in a large cohort of older women. METHODS: Data were analysed from women included in the Study of Osteoporotic Fractures, a cohort of community-dwelling women aged ≥65 years at enrolment. Serum 25-hydroxyvitamin D concentration was assessed at the year 6 visit, as were BMI and other factors associated with vitamin D and/or diabetes. Diabetes status was determined at each subsequent visit by self-report and medication use. Only those without prevalent diabetes at the year 6 visit were included in the present analysis (N = 5463, mean age 76.5 years). RESULTS: During a mean ±sd follow-up of 8.6 ± 4.4 years, incident diabetes was reported in 320 participants. The mean BMI was higher in those with a 25-hydroxyvitamin D concentration <20 ng/ml (<50 nmol/l) than in those with concentrations 20-30 or ≥30 ng/ml [50-74 or ≥75 nmol/l (P < 0.0001)]. A higher 25-hydroxyvitamin D concentration was associated with a 13% lower risk of incident diabetes after adjustment for age and clinic site [hazard ratio 0.87, 95% CI 0.76-0.99, per sd increase in 25-hydroxyvitamin D]; however, the addition of BMI to the model attenuated the estimated effect (hazard ratio 0.97, 95% CI 0.86-1.11). Adjustment for additional potential confounders yielded similar results. CONCLUSIONS: Serum 25-hydroxyvitamin D does not independently predict incident diabetes in older women. Although those with higher 25-hydroxyvitamin D concentrations are less likely to develop diabetes, this is mainly explained by their lower BMI.

Postmenopausal women treated with combination parathyroid hormone (1-84) and ibandronate demonstrate different microstructural changes at the radius vs. tibia: the PTH and Ibandronate Combination Study (PICS).

SUMMARY: In postmenopausal women receiving combination parathyroid hormone (PTH) (1-84) therapy and ibandronate, we evaluated bone microarchitecture and biomechanics using high-resolution peripheral quantitative computed tomography (HR-pQCT). Cortical and trabecular changes were different at the nonweight-bearing radius vs. the weight-bearing tibia, with more favorable overall changes at the tibia. INTRODUCTION: PTH therapy and bisphosphonates decrease fracture risk in postmenopausal osteoporosis, but their effects on bone microstructure and strength have not been fully characterized, particularly during combination therapy. PTH increases trabecular bone mineral density (BMD) substantially but may decrease cortical BMD, possibly by stimulating intracortical remodeling. We evaluated bone microarchitecture and biomechanics with HR-pQCT at the radius (a nonweight-bearing site) and tibia (weight bearing) in women receiving combination PTH(1-84) and ibandronate. METHODS: Postmenopausal women with low bone mass (n = 43) were treated with 6 months of PTH(1-84) (100 µg/day), either as one 6- or two 3-month courses, in combination with ibandronate (150 mg/month) over 2 years. HR-pQCT was performed before and after therapy. RESULTS: Because changes in HR-pQCT parameters did not differ between treatment arms, groups were pooled into one cohort for analysis. Trabecular BMD increased at both radius and tibia (p < 0.01 for each). Cortical thickness and BMD decreased at the radius (p < 0.01), consistent with changes in dual-energy X-ray absorptiometry, while these parameters did not change at the tibia (p ≤ 0.02 for difference between radius and tibia). In contrast, cortical porosity increased at the tibia (p < 0.01) but not radius. Stiffness and failure load decreased at the radius (p < 0.0001) but did not change at the tibia. CONCLUSIONS: Cortical and trabecular changes in response to the PTH/ibandronate treatment combinations utilized in this study were different at the nonweight-bearing radius vs. the weight-bearing tibia, with more favorable overall changes at the tibia. Our findings support the possibility that weight bearing may optimize the effects of osteoporosis therapy.

Laboratory reproducibility of biochemical markers of bone turnover in clinical practice.

SUMMARY: To determine the laboratory reproducibility of urine N-telopeptide and serum bone-specific alkaline phosphatase measurements, we sent identical specimens to six US commercial labs over an 8-month period. Longitudinal and within-run laboratory reproducibility varied substantially. Efforts to improve the reproducibility of these tests are needed. INTRODUCTION: We assessed the laboratory reproducibility of urine N-telopeptide (NTX) and serum bone-specific alkaline phosphatase (BAP). METHODS: Serum and urine were collected from five postmenopausal women, pooled, divided into identical aliquots, and frozen. To evaluate longitudinal reproducibility, identical specimens were sent to six US commercial labs on five dates over an 8-month period. To evaluate within-run reproducibility, on the fifth date, each lab was sent five identical specimens. Labs were unaware of the investigation. RESULTS: Longitudinal coefficients of variation (CVs) ranged from 5.4% to 37.6% for NTX and from 3.1% to 23.6% for BAP. Within-run CVs ranged from 1.5% to 17.2% for NTX. Compared to the Osteomark NTX assay, the Vitros ECi NTX assay had significantly higher longitudinal reproducibility (mean CV 7.2% vs. 30.3%, p < 0.0005) and within-run reproducibility (mean CV 3.5% vs. 12.7%, p < 0.0005). CONCLUSIONS: Reproducibility of urine NTX and serum BAP varies substantially across US labs.

High prevalence of anti-alpha-crystallin antibodies in multiple sclerosis: correlation with severity and activity of disease.

INTRODUCTION: The presence of T-cell reactivity to alphaB-crystallin in patients with multiple sclerosis (MS) has suggested that this small molecular weight heat shock protein (Hsp) may be an autoantigen in MS. MATERIAL AND METHODS: We have tested the serum of patients with clinically definite MS (n=30), other inflammatory neurological disease (n=22), non-inflammatory neurological disease (n=42) and healthy individuals (n=23) for systemic humoral responses to bovine alphaB-crystallin, to the homologous chaperone protein, alphaA-crystallin, and to another small Hsp, Hsp 27. RESULTS: Sixty-three percent of MS patients exhibited immunoreactivity to alpha-crystallin and this was present in all 4 of 4 non-ambulatory patients with MS. In contrast, serum concentrations in MS patients of antibodies to the small Hsp, Hsp27, and to myelin basic protein were negligible (P<0.001). Serum anti-alpha-crystallin immune responses were detected in significantly lower percentages of patients with other inflammatory neurological diseases (32%, P<0.025), and with non-inflammatory neurological diseases (12%, P<0.001). None of the healthy control individuals showed anti-alpha-crystallin reactivity. The concentration of anti-alpha-crystallin antibodies in patients with MS correlated with severe disease (P<0.05) and with active disease (P<0.025). CONCLUSION: Our observations support the notion that anti-alpha-crystallin autoimmune responses may contribute to pathogenicity in MS and may represent a mechanism of how recurrent attacks of MS develop subsequent to an isolated demyelinating episode.