Calcium and Bone Turnover Markers in Acromegaly: A Prospective, Controlled Study

Context: Acromegaly has been associated with calcium-phosphate and bone turnover alterations. Controlled studies of these interactions are sparse. Objective: To evaluate calcium and bone metabolism in active and treated acromegaly. Design/Setting/Patients:We conducted a controlled, prospective study at a tertiary referral center. We studied 22 patients with acromegaly referred for surgical or medical therapy (ACM) and 22 with nonfunctioning pituitary adenomas referred for surgery (control). Main OutcomeMeasures:Calcium (serum and urine), phosphorus, parathyroid hormone (PTH), 25-hydroxy- and 1,25-dihydroxy-vitamin D, bone turnover markers [serum C-terminal telopeptide of type 1 collagen (CTX) and procollagen type 1 N-terminal propeptide (P1NP)], and cytokines [receptor activator of nuclear factor kappa B ligand (RANK-L) and osteoprotegerin (OPG)] at baseline and 3 to 6 months after treatment. Results: At baseline, the ACM group had lower PTH levels than controls (36.3 +/- 13.9 pg/mL vs 56.0 +/- 19.9 pg/mL) and higher phosphorus (4.34 +/- 0.71 mg/dL vs 3.55 +/- 0.50 mg/dL) (P < 0.01). Groups had similar levels of serum and urine calcium and 25-hydroxy- and 1,25-dihydroxy-vitamin D. The ACM group had higher bone turnover markers than control; P1NP and CTX were strongly correlated (r(2) = 0.82, P < 0.05). CTX was dependent on age and disease group but not on sex or gonadal status. After treatment of acromegaly, serum calcium (9.52 +/- 0.43 mg/dL to 9.26 +/- 0.28 mg/dL), phosphorus (4.34 +/- 0.71 mg/dL to 3.90 +/- 0.80 mg/dL), and CTX (0.91 +/- 0.75 ng/mL to 0.63 +/- 0.68 ng/mL) decreased, while PTH increased (36.3 +/- 13.9 pg/mL to 48.9 +/- 16.7 pg/mL) (P < 0.01). 25-hydroxy-vitamin D, P1NP, and RANK-L/OPG ratio did not change significantly. Conclusions: Acromegaly patients exhibited PTH-independent calcium-phosphate alterations and enhanced coupled bone formation and resorption. Within 6 months of treatment, bone resorption decreased, whereas RANK-L/OPG changes were inconsistent.