In Acromegaly, Increased Bone Mineral Density (BMD) is Determined by GH-excess, Gonadal Function and Gender

Objectives: The aim of our study was to evaluate bone metabolism and bone mineral density (BMD), and to indicate the main determinants of these parameters in a large group of patients with active acromegaly.

Methods: A group of 121 active acromegalics, aged 23-80 years, from a single endocrinological center was studied. Serum GH, IGF-I, LH, FSH, PRL, estradiol/testosterone, osteocalcin (OC), type I collagen carboxyterminal telopeptide (ICTP) as well as BMD by DXA at spine L2-L4, femoral neck, Ward's triangle and trochanter were measured.

Results: Serum OC and ICTP concentrations were elevated (mean+/-SEM: 31.7+/-2.2 microg/L, p<0.001; 7.3+/-0.5 microg/L, p<0.001, respectively), and positively correlated with each other, as well as with IGF-I. BMD (Z-scores) was increased at L2-L4, femoral neck and trochanter (0.35+/-0.15, p=0.016; 0.60+/-0.11, p<0.001 and 0.59+/-0.13, p<0.001; respectively). The main determinants of Z-scores and ICTP were gonadal status and gender, while of OC was IGF-I. Eugonadal acromegalics had higher than normal serum OC and ICTP, as well as Z-scores at all measured sites. Hypogonadal patients (2/3 of the population) had significantly higher serum ICTP concentrations and lower BMD at all sites, when compared to eugonadal acromegalics. Thirty five percent of hypogonadal subjects had T-score<-1. Men had significantly higher serum ICTP and lower Z-scores than women.

Conclusions: (i) In active acromegaly, enhanced IGF-I-dependent bone turnover and increased BMD is observed. (ii) In hypogonadal acromegalics, high bone resorption decreases BMD and may lead to osteoporosis. (iii) There is a smaller increase in bone resorption and greater increase in BMD in women with acromegaly than in men.