Relation of RANKL and OPG Levels with Bone Resorption in Patients with Acromegaly and Prolactinoma

Abstract

The objective of this study was to investigate the effect of hyperprolactinemia and high levels of insulin-like growth factor-I (IGF-I) on bone resorption and their relation with receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin (OPG) in patients with prolactinoma and acromegaly. Thirty-one patients with acromegaly, 28 patients with prolactinoma, and 33 healthy individuals were included in the study. Serum concentrations of RANKL, OPG, bone alkaline phosphatase (bone ALP), osteocalcin (OC), C-terminal telopeptide of type 1 collagen (CTX), procollagen type 1 N-terminal propeptide (P1NP) and urine deoxypyridinoline (DPD) levels were detected and bone mineral density (BMD) was measured. Groups were not statistically different from each other with regard to serum levels of RANKL and OPG. The RANKL/OPG ratio was higher in the prolactinoma group than in the control group (p=0.046). A positive correlation between OPG and increasing age was detected in both the prolactinoma and control groups (r=0.524, p=0.004 and r=0.380, p=0.029, respectively). An inverse correlation was observed between IGF-I and OPG after excluding age in the prolactinoma group (r=-0.412, p=0.046). OC and bone ALP were negatively associated with RANKL in the acromegaly group (r=-0.384, p=0.036 and r=-0.528, p=0.003, respectively). There was an inverse correlation between OPG and BMD at the femoral neck in the acromegaly group (r=-0.422, p=0.02). The effect of IGF-I on bone remodeling may be partly mediated by RANKL and OPG. The RANKL/OPG ratio plays an important role in prolactinoma. A positive correlation of OPG with age and an inverse correlation with IGF-I favor the compensatory response of OPG against bone loss in the aging skeleton.

Hyperprolactinaemia

“…PRL within the physiological range stimulates bone formation, mild hyperprolactinaemia increases bone resorption, and marked hyperprolactinaemia further increases bone resorption and inhibits bone formation [77]. This is supported by findings that patients with prolactinoma have suppressed osteocalcin, high NTX (collagen type I crosslinked N-telopeptide), and increased RANKL (receptor activator of nuclear factor-kB ligand)/OPG (osteoprotegerin) ratio, suggesting increased bone resorption and decreased bone formation [77,78]. The relative contribution of hypogonadotropic hypogonadism and hyperprolactinemia is controversial and it has been hypothesized that these mechanisms have synergistic effects on bone loss [77].…”

MANAGEMENT OF ENDOCRINE DISEASE: Bone disorders associated with acromegaly: mechanisms and treatment

“…The increased bone turnover is directly related to the levels of circulating GH and IGF-I (40). The increased bone remodeling is likely due to the actions of IGF-I on the induction of RANKL leading to enhanced osteoclastogenesis (40,72,73). Analyzing gene expression in sphenoid bone tissue samples of subjects with acromegaly, Belaya et al suggested that GH excess may induce mesenchymal stem cell commitment toward cartilage or adipocytes instead of toward mature osteoblasts (74).…”

Italian Association of Clinical Endocrinologists (AME) and International Chapter of Clinical Endocrinology (ICCE). Position statement for clinical practice: prolactin-secreting tumors

“…Hyperprolactinemia per se or through hypogonadism induces an increased bone turnover, with a predominance of bone resorption and, consequently, an increased occurrence of osteopenia and osteoporosis ( 11 , 36 , 37 , 38 ). Suppressed levels of osteocalcin (OC), high collagen type I crosslinked N-telopeptide (NTX), and increased receptor activator of nuclear factor-kB ligand (RANKL)/osteoprotegerin ratio have been reported in patients with prolactinoma ( 39 , 40 ). Both in females and in males, trabecular bone in the spine and in the hip is more affected than cortical bone in the distal radium; in fact, spinal bone mineral content is generally reduced from 20 to 30% and forearm bone mineral content from 2.5 to 10% ( 41 ).…”