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

J Clin Endocrinol Metab. 2017 Jul 1;102(7):2416-2424. doi: 10.1210/jc.2016-3693.

Abstract

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 outcome measures: 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 κB 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 (r2 = 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.

Conclusion: 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.

Trial registration: ClinicalTrials.gov NCT01568359.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acromegaly / blood
  • Acromegaly / diagnosis*
  • Acromegaly / therapy*
  • Adult
  • Analysis of Variance
  • Bone Remodeling / physiology
  • Bone Resorption / physiopathology
  • Bone and Bones / metabolism*
  • Calcium Phosphates / metabolism*
  • Case-Control Studies
  • Female
  • Humans
  • Male
  • Middle Aged
  • Parathyroid Hormone / metabolism*
  • Prognosis
  • Prospective Studies
  • Regression Analysis
  • Severity of Illness Index
  • Somatostatin / therapeutic use
  • Statistics, Nonparametric
  • Young Adult

Substances

  • Calcium Phosphates
  • Parathyroid Hormone
  • Somatostatin
  • calcium phosphate

Associated data

  • ClinicalTrials.gov/NCT01568359