Bone mineral density and turnover in patients with acromegaly in relation to sex, disease activity, and gonadal function

Abstract

Acromegaly is a rare disease caused by growth hormone (GH) hypersecretion. GH and insulin-like growth factor-I (IGF-I) exert anabolic activity in bones. Nevertheless, bone mineral density (BMD) loss is not uncommon in patients with acromegaly. It is assumed to be due to hypogonadism associated with the acromegaly. The aim of the study was to examine BMD at various skeletal sites and bone turnover and to assess the influence of impaired gonadal function and disease activity on BMD and turnover changes in acromegaly. A total of 62 patients were studied (40 women, 22 men). Among the women, 22 had active disease and 18 were cured; 16 women had normal gonadal function, and 24 were hypogonadal. Altogether, 12 men presented with active acromegaly, and 10 were cured; normal gonadal function was found in 10 men, and hypogonadism was diagnosed in 12 men. Controls were 30 healthy subjects. Densitometry using dual-energy X-ray absorptiometry of the lumbar spine, proximal femur, forearm, and total body was carried out. Bone turnover was studied based on serum osteocalcin, C-terminal collagen type 1 crosslinks, and bone alkaline phosphatase concentration. A disadvantageous effect of acromegaly on bone density was associated with hypogonadism in the distal radius (in women), the proximal femur (in men), and the total body (both sexes). An anabolic effect of GH during active acromegaly was present in the proximal femur only in men. We confirmed increased bone turnover in the presence of acromegaly, and these changes were similar regarding the activity of the disease and the gonadal status.

Treatment of acromegaly increases BMD but reduces trabecular bone score: a longitudinal study

“…The biochemical markers reflect bone resorption (CTX-1) and formation (P1NP) and together they describe bone turnover (11,27).…”

“…Bone remodeling is coupled in as well active acromegaly as following treatment (11), in contrast to for instance endogenous Cushing's syndrome, where bone resorption and formation are uncoupled in the active state, becoming coupled following treatment and remission (36). It is therefore to be expected that disease control in acromegaly will be followed by a decrease in bone turnover and a filling of the remodeling space followed by a relative increase in BMD (11,27), as seen in other endocrine disorders with coupled bone remodeling, following treatment (37,38). The decrease in TBS following treatment in this study, despite the increase in BMD, reflects that the two measures describe different properties of bone, especially in other conditions than postmenopausal osteoporosis (4), but are in alignment with the observed high incidence and prevalence of vertebral fractures seen in acromegaly (5,31,32,33,34).…”

High prevalence of vertebral fractures despite normal bone mineral density in patients with long-term controlled acromegaly

“…It has also been suggested that the anabolic effects of GH on bone mineral density (BMD) may be sustained after cure of acromegaly (1)(2)(3)(4)(5), but duration of follow-up was relatively short in the majority of studies. The effects of GH excess on BMD appear to be less consistent.…”

“…In active acromegaly, high circulating concentrations of GH and IGF1 are associated with increased cortical BMD (6)(7)(8)(9)(10). The reported effects of GH/IGF1 excess on trabecular BMD are more variable, with studies reporting either increased or decreased BMD at trabecular sites possibly due to the variable presence of hypogonadism (1,(3)(4)(5)(11)(12)(13).…”

Serum GH and IGF-I are significant determinants of bone turnover but not bone mineral density in active acromegaly: a prospective study of more than 70 consecutive patients

“…Bone turnover is increased, suggesting activation of both osteoblasts and osteoclasts in active acromegaly (1)(2)(3)(4)(5)(6)(7). Moreover, biochemical markers of bone formation and bone resorption correlate with circulating GH and IGF-I levels suggesting that GH and liver-derived IGF-I may have direct effects on both cell types in modulating turnover (1,2,8,9).…”