Sclerostin in institutionalized elderly women: associations with quantitative bone ultrasound, bone turnover, fractures, and mortality.

OBJECTIVES: To evaluate the association between levels of circulating sclerostin (an emerging biomarker and important regulator of bone formation) and laboratory parameters of bone and mineral metabolism, bone mineral density and quality measured using quantitative ultrasound (QUS), fracture risk, and mortality. DESIGN: Prospective cohort study. SETTING: Austrian nursing homes (N = 95). PARTICIPANTS: Female nursing home residents aged 70 and older (mean 84 ± 6; N = 539). MEASUREMENTS: Serum sclerostin, bone turnover markers, and bone mineral density and quality were measured at baseline. Participants were followed for clinical fractures and all-cause mortality. RESULTS: Partial correlation analysis adjusted for age, weight, and renal function revealed a significant positive correlation between sclerostin levels and calcaneal stiffness and radial and phalangeal speed of sound (all P < .01) and a significant negative correlation between sclerostin levels and osteocalcin, serum C-terminal telopeptide of type I collagen, and parathyroid hormone (PTH; P < .05). After a mean follow-up of 27 ± 8 months, 139 participants (26%) had died and 64 had a hip or other nonvertebral fracture (12%). Sclerostin was not predictive of mortality. In women with a negative fracture history, it was significantly but not linearly associated with fracture risk. CONCLUSION: In institutionalized elderly women, there is a significant relationship between serum sclerostin levels and QUS indices, bone turnover, and PTH, but sclerostin was not strongly associated with important clinical outcomes. Thus, it remains unclear whether sclerostin is a clinically useful predictor of fractures or mortality, at least in this setting.

Low 25-hydroxyvitamin D is associated with increased mortality in female nursing home residents.

CONTEXT: Vitamin D deficiency contributes to skeletal diseases and is highly prevalent among institutionalized elderly patients. Whether low 25-hydroxyvitamin D (25[OH]D) concentrations are an independent risk factor for mortality in these patients is, however, unclear. OBJECTIVE: We aimed to evaluate whether 25(OH)D concentrations are associated with mortality. DESIGN, SETTING, AND PARTICIPANTS: This is a prospective cohort study among elderly female patients (age >70 yr) recruited from 95 nursing homes in Austria. MAIN OUTCOME MEASURES: We calculated Cox proportional hazard ratios (HR) for all-cause mortality according to 25(OH)D quartiles. RESULTS: We examined 961 study participants (age 83.7 ± 6.1 yr). Median 25(OH)D concentration was 17.5 (interquartile range 13.7-25.5) nmol/liter, and 93% of our cohort had 25(OH)D levels below 50 nmol/liter. During a mean follow-up time of 27 ± 8 months, 284 patients died. Compared with the fourth quartile (25[OH]D >25.5 nmol/liter), the age-adjusted HR (with 95% confidence interval) was 1.49 (1.07-2.10) in the first 25(OH)D quartile (25[OH]D <14.0 nmol/liter), and this association remained significant after multivariate adjustments (HR = 1.56; 95% confidence interval = 1.01-2.40). CONCLUSIONS: This Austrian study suggests that the majority of institutionalized female patients are vitamin D deficient during winter and that there was an inverse association of 25(OH)D and mortality. These data underscore the urgent need for effective strategies for the prevention and treatment of vitamin D deficiency, in particular in the setting of nursing homes.

Serum osteoprotegerin levels in patients after liver transplantation and correlation to bone turnover, bone mineral density and fracture status.

The aim of this cross sectional study was to evaluate the prevalence of osteoporosis, vertebral fracture status and possible risk factors of bone loss including serum osteoprotegerin, a novel key regulator of osteoclast proliferation and activity in the posttransplantation period. We investigated 15 patients (10 male, 5 female) 20 +/- 6 (SE) months after orthotopic liver transplantation (OLT). All patients received immunosuppressive therapy and non were on calcium and/or vitamin D supplements at the time of admission to our osteoporosis outpatient clinic. Examinations included a bone densitometry measurement at the femoral neck, a standardized spinal X-ray and a morning blood sample. According to WHO criteria, osteoporosis at the femoral neck was present in 67% (10/15) of the patients with a mean T-score of -2.55 +/- 0.35. Vertebral fractures were seen in 33% and the mean number of fractures was 2.4 per patient. Secondary hyperparathyroidism (33%), vitamin D deficiency (53%) as well as impaired renal function (47%) were frequent findings in the patients. Low serum calcium was associated with elevated PTH- (r = -0.75, p = 0.001), serum cross laps- (r = -0.61, p = 0.01), osteocalcin levels (r = -0.49, p = 0.05), was an independent predictor of femoral neck bone mass (r = 0.57, p = 0.02) and accounted for 36% of this variance. Similarly, serum magnesium levels were also independently correlated to femoral neck Z-scores (r = -0.68, p = 0.0005). Two-thirds of the patients had elevated serum cross-laps, osteocalcin and bone specific alkaline phosphatase levels reflecting increased bone turnover. Serum osteoprotegerin (OPG) in liver transplant recipients was not significantly different when compared to healthy, matched controls (84.7 +/- 6.6 vs. 97.3 +/- 9.4 pg/ml, p = 0.50) and similar when fractured/non-fractured or osteoporotic/non-osteoporotic patients were compared. Serum OPG was, however, significantly correlated to serum cross laps (r = 0.71, p = 0.003), osteocalcin (r = 0.63, p = 0.01), serum parathyroid hormone (r = 0.61, p = 0.01) and serum creatinine levels (r = 0.53, p = 0.04) and showed only a weak and non-significant correlation to femoral neck Z-scores (r = -0.38, p = 0.16). Multiple regression analysis revealed that serum OPG was correlated independently of PTH, serum calcium and creatinine to serum cross-laps concentrations (r = 0.63, p = 0.04). In summary, we found a high prevalence of osteoporosis and vertebral fractures in liver transplant recipients with many of the patients showing evidence of vitamin D deficiency, secondary hyperparathyroidism and accelerated bone turnover. We conclude that secondary hyperparathyroidism and possibly serum magnesium seems to contribute significantly to the changes in bone mass during the posttransplantation period. Serum OPG was not correlated to bone mass or fracture status in this cross sectional setting but was elevated together with other bone resorption and -formation markers.