BIOCHEMICAL ASSESSMENT OF BONE-FORMATION AND RESORPTION IN ACROMEGALY

The effects of chronic GH and insulin-like growth factor-I (IGF-I) exc ess on bone metabolism were examined by measuring serum markers of bon e formation and urine markers of bone resorption as well as vertebral bone densities in patients with active acromegaly. Fasting serum GH le vels were elevated in all 27 patients (31 +/- 11 mug/L). Serum calcium levels were within the normal range, except in 3 of 27 (10%) patients with mild hypercalcemia. Urinary calcium excretion, however, was incr eased in 6 (22%) patients despite mainly normal serum PTH and 1,25-dih ydroxyvitamin D levels, suggesting a direct renal GH and/or IGF-1-medi ated calciuric effect. Urinary hydroxyproline/creatinine excretion was increased in all except 1 patient and correlated with plasma IGF-I le vels (r = 0.49; P < 0.02; n = 22). A more specific indicator of bone c ollagen turnover, urinary type I collagen cross-linked N-telopeptide, was elevated in all except 1 patient and correlated with serum GH (r = 0.47; P < 0.02), IGF-I (r = 0.60; P < 0.005), and urinary hydroxyprol ine/creatinine excretion (r = 0.62; P < 0.001). Serum bone Gla protein (osteocalcin), a specific marker of osteoblastic activity, was also i ncreased in 50% of the patients and correlated with urinary N-telopept ide (r = 0.47; P < 0.02), but not with serum GH or IGF-I concentration s. Trabecular bone density, as determined by quantitative computerized tomography of the lumbar spine, was increased in only 1 patient; 13 o thers had subnormal bone density. The results suggest that in long-sta nding acromegaly, osteoblastic and osteoclastic activities are increas ed. Vertebral trabecular bone mass is usually reduced. Urinary collage n cross-links may serve as a more specific marker of bone resorption i n acromegaly.