Recombinant Human Parathyroid Hormone Effect on Health-Related Quality of Life in Adults With Chronic Hypoparathyroidism

Context: Reduced health-related quality of life (HRQoL) is common in patients with hypoparathyroidism on conventional therapy with calcium and active vitamin D supplements. Objective: To examine the effects of recombinant human parathyroid hormone (rhPTH[1-84]) on HRQoL as measured by the 36-Item Short Form Health Survey (SF-36) during the multinational, randomized, placebo-controlled REPLACE study. Patients: 122 adults with chronic hypoparathyroidism. Intervention(s): Following an optimization period when calcium and/or active vitamin D supplements were adjusted to reach target serum calcium levels (8.0-9.0 mg/dL; 2.0-2.2 mmol/L), patients were randomized to receive placebo (n=39) or rhPTH(1-84) (n=83) (starting dose 50 mug/day, could be titrated up to 100 mug/day); supplement doses were adjusted to maintain target serum calcium levels. Main Outcome Measure(s): Change from baseline (post-optimization, at randomization) to Week 24 in HRQoL as assessed by the SF-36v2 health survey. Results: Overall, the between-group differences were not statistically significant. However, in the rhPTH(1-84) group, there were significant improvements in the physical component summary score (P=0.004) and in body pain (P<0.05), general health (P<0.05), and vitality (P<0.001) domains as compared with baseline values. In the placebo group, there were no significant changes for any of the domains. The magnitude of change between 0 and 24 weeks in SF-36 scores was negatively correlated with baseline scores, such that patients with lower HRQoL at baseline were more likely to experience improvement in response to treatment. Conclusions: Treatment with rhPTH(1-84) may improve HRQoL in adults with hypoparathyroidism

Bone Mineral Density, Bone Turnover, and Systemic Inflammation in Non-cirrhotics with Chronic Hepatitis C

Background: Whether chronic HCV, a disease characterized by systemic inflammation, impacts bone mineral density (BMD) independent of cirrhosis is unknown. Aim: We aimed to evaluate the association between BMD, systemic inflammation, and markers of bone turnover in chronic HCV without cirrhosis. Methods: Non-cirrhotics, 40–60&nbsp;years old, with chronic HCV underwent measurement of: (1) BMD by dual-energy X-ray absorptiometry scan and (2) serum markers of systemic inflammation and bone turnover. By Chi-squared or t test, we compared those with normal versus low BMD. Results: Of the 60 non-cirrhotics, 53&nbsp;% were female and 53&nbsp;% Caucasian. Mean (SD) age was 53.3&nbsp;years (5.7), total bilirubin 0.7&nbsp;mg/dL (0.3), creatinine 0.8&nbsp;mg/dL (0.2), and body mass index 28.4&nbsp;kg/m2 (6.5). Low BMD was observed in 42&nbsp;%: 30&nbsp;% had osteopenia, 12&nbsp;% had osteoporosis. Elevated tumor necrosis factor α, interleukin-6, and C-reactive protein levels were found in 26, 32, and 5&nbsp;%, respectively, but did not differ by BMD group (p&nbsp;&gt;&nbsp;0.05). Patients with low BMD had higher serum phosphorus (4.1 vs. 3.5&nbsp;mg/dL) and pro-peptide of type 1 collagen (P1NP; 73.1 vs. 47.5&nbsp;ng/mL) [p&nbsp;&lt;&nbsp;0.05], but similar bone-specific alkaline phosphatase, serum C-telopeptide, and parathyroid hormone levels. Conclusions: Low BMD is prevalent in 40- to 60-year-old non-cirrhotics with chronic HCV, but not associated with systemic inflammatory markers. Elevated P1NP levels may help to identify those at increased risk of bone complications in this population. Chronic HCV should be considered a risk factor for bone loss, prompting earlier BMD assessments in both men and women

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&lt;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&lt;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