Skeletal Involvement in Female Acromegalic Subjects: The Effects of Growth Hormone Excess in Amenorrheal and Menstruating Patients

Abstract

Bone involvement is a common clinical feature in acromegalic patients, though previous studies gave divergent results possibly because of the different gonadal status of the patients studied. To study the influence of estrogen milieu in these patients, we evaluated 23 acromegalic patients with active disease, subdivided into two groups: menstruating and amenorrheal patients, comparable for duration and activity of disease. Forty-two matched women served as controls. Skeletal involvement was studied by measuring: (a) the main biomarkers of bone turnover: serum alkaline phosphatase total activity (AP), bone GLA protein (BGP), serum carboxy-terminal propeptide of type I collagen (PICP), serum type I cross-linked N-telopeptide (ICTP), and urinary pyridinoline and deoxypyridinoline corrected for creatinine (Pyr/Cr, D-Pyr/Cr) and urinary calcium/creatinine ratio (Ca/Cr); (b) bone mineral density (BMD), as measured by quantitative computed tomography both at lumbar spine and distal radius, and by dual X-ray absorptiometry both at lumbar spine and at three femoral sites (Ward's triangle, femoral neck, and great trochanter). AP, BGP, ICTP, Pyr/Cr, D-Pyr/Cr were significantly higher in patients than in controls, independent of the menstrual pattern. Higher PICP levels were found in the whole group and in menstruating acromegalics when compared with control women; no difference was found in amenorrheal patients, who in turn showed higher urinary Ca/Cr values. When patients were considered all together, BMD at spine, femoral neck, and trochanter was higher than in controls. In contrast, when the gonadal status was taking into account and, menstruating and amenorrheal subjects were considered separately, BMD at spine, but not in other sites, was significantly higher in menstruating patients than in controls. In contrast, no difference of BMD values at any site was observed between amenorrheal patients and controls. The mean BMD Z scores allowed us to detect an unequal involvement of different skeletal sites. Our results show that bone turnover is increased in acromegalic women and suggest that GH anabolic effect on bone is more evident in the presence of estrogens and that different skeletal sites may be affected differently by hormone

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

“…Previous studies show poor correlation between biochemical markers of bone turnover and bone remodeling at the tissue level as given by histomorphometry (5). In contrast to some previous studies (7,13,15), but in agreement with others (4, 6, 19), we found no effect of gonadal status, regardless of gender, on bone mass or BMD in acromegalic patients in this study. In general, the Z-scores were lower in hypogonadal patients and the lack of significance could be due to a type 2 error (n to small).…”

“…Details on gonadal status in patients and controls are given in Table 1. The duration of acromegaly (nZ55) was estimated to be (mean and range) 8 years (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20). The study was approved by the local ethical committee and conducted according to the Declaration of Helsinki II.…”

“…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).…”

“…However, a recent study demonstrated a high prevalence of vertebral fractures in postmenopausal women with acromegaly in relation to disease activity (21). Thus, gonadal status has been proposed to be an important determinant of excess GH (7,13,15,17), and it is possible that trabecular bone, with its more intimate contact with the circulation, is influenced by sex steroids to a greater extent.…”

Bone and joint alterations in acromegaly

“…Furthermore, these effects are gender-independent. The same authors [35] reported that bone density forearm is normal, while bone density in the femur increases independently of the gonadal status; moreover an increased bone mass can be documented in the spine, but not in the femur or in the forearm in eugonadal patients, while hypogonadal patients have values of trabecular bone mass at both sites similar to those in the matched controls. Other authors reported increased BMD in eugonadal acromegalic patients, at both femoral and lumbar spine levels [36].…”