Lower fracture risk in older men with higher sclerostin concentration: A prospective analysis from the MINOS study

Abstract

Sclerostin is synthesized by osteocytes and inhibits bone formation. We measured serum sclerostin levels in 710 men aged 50 years and older. Bone mineral density (BMD) was measured at the lumbar spine, hip, and distal forearm. Serum sclerostin increased with age (unadjusted r ¼ 0.30, p < 0.001). After adjustment for age, weight, and bioavailable 17b-estradiol, serum sclerostin correlated positively with BMD (r ¼ 0.24 to 0.35, p < 0.001) and negatively with the levels of bone turnover markers (r ¼ À0.09 to À0.23, p < 0.05 to 0.001). During a 10-year follow-up, 75 men sustained fragility fractures. Fracture risk was lower in the two upper quintiles of sclerostin combined versus three lower quintiles combined (6.1 versus 13.5%, p < 0.01). We compared fracture risk in the two highest quintiles combined versus three lower quintiles combined using the Cox model adjusted for age, weight, leisure physical activity, BMD, bone width (tubular bones), prevalent fracture, prevalent falls, ischemic heart disease, and severe abdominal aortic calcification. Men with higher sclerostin concentration had lower fracture risk (adjusted for hip BMD, hazard ratio [HR] ¼ 0.55, 95% confidence interval [CI] 0.31 to 0.96, p < 0.05). The results were similar in 47 men with major fragility fractures (adjusted for lumbar spine BMD: HR ¼ 0.39, 95% CI 0.17 to 0.90, p < 0.05). Men who had higher sclerostin and higher BMD (two highest quintiles) had lower risk of fracture compared with men who had lower BMD and lower sclerostin levels (three lower quintiles) (HR ¼ 0.24, 95% CI 0.10 to 0.62, p < 0.005). Circulating sclerostin was not associated with mortality rate or the incidence of major cardiovascular events. Thus, in older men, higher serum sclerostin levels are associated with lower risk of fracture, higher BMD, and lower bone turnover rate. ß

Gender differences in sclerostin and clinical characteristics in type 1 diabetes mellitus

“…The latter is consistent with the data reported by Gennari et al (16) using DXA, although an association between sclerostin serum levels and DXA measurements was also described in T1DM (17). Besides BMD, in previous works, sclerostin was associated with fracture risk, although etherogeneus results were reported (31,32). In particular, sclerostin was related to vertebral fractures in T2DM (33).…”

“…A reduced bone formation as a consequence of reduced osteoblast activity has been identified as the mean pathogenetic effect or for low bone mineral density (BMD) in subjects with T1DM (1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39). intimal thickening in atherosclerosis, and Wnt/b-catenin signaling is a regulator of VSMC behavior (9).…”

Serum sclerostin levels in men with idiopathic osteoporosis

“…Corroborating previous findings (5,7,8,9,16), we also found a strong positive association between serum sclerostin levels and age. Several in vivo studies have shown that mechanical loading decreases, whereas unloading increases local sclerostin production (17,18,19).…”

“…Although not unequivocally (7,16), earlier studies have also reported positive associations between serum sclerostin levels and bone mass in both men and women (5,7,8). These positive associations between bone mass, other parameters of bone strength, and serum sclerostin levels may seem counterintuitive since sclerostin is considered to inhibit bone formation.…”

“…Serum levels of sclerostin increase with aging, have been reported to be positively related to overall bone mass, and sex differences have been described (5,6,7,8). Furthermore, observational and interventional data suggest that circulating sclerostin levels are modulated by estrogen exposure (6,7,8,9).…”