Acute changes in serum osteoprotegerin and receptor activator for nuclear factor-κB ligand levels in women with established osteoporosis treated with teriparatide

Abstract

Objective: The mechanisms regulating the anabolic response of the skeleton to intermittent exogenous parathyroid hormone (PTH) administration are not fully elucidated. The aim of this prospective study was to evaluate the acute effect (up to 1 month) of teriparatide (TPTD; human recombinant PTH 1-34) on serum levels of osteoprotegerin (OPG) and receptor activator for nuclear factor-kB ligand (RANKL) in women with established osteoporosis. Design: Twenty-three postmenopausal Caucasian women with established osteoporosis (mean age 66.7G1.6 years) received daily injections of 20 mg TPTD for 12 months. Methods: Serum samples for total calcium (Ca), phosphate, alkaline phosphatase, N-terminal propeptide of type I collagen, intact PTH (iPTH), OPG, and RANKL were obtained at baseline, 1 h, 1 day, and 1 month after initiation of therapy. Lumbar spine bone mineral density (BMD) was measured before and 12 months after TPTD treatment. Results: Serum total Ca increased and iPTH gradually decreased with TPTD treatment. Serum OPG levels remained unchanged, while RANKL increased gradually during the study (P!0.001). There was no correlation between OPG or RANKL and BMD changes or iPTH levels. Conclusions: TPTD therapy in women with postmenopausal osteoporosis results in acute increase in serum RANKL levels but does not affect serum OPG. These changes may reflect an increase in the number of active osteoblasts with therapy and might be responsible for the acceleration of bone turnover rate that characterizes TPTD. European Journal of Endocrinology 158 411-415

Serum RANKL, osteoprotegerin (OPG), and RANKL/OPG ratio in nephrotic children

“…Secondly, serum RANKL and OPG may not reflect the levels and activity of these cytokines in the bone microenvironment, since a small amount of locally acting cytokines leak to systemic circulation [41], and a part of serum OPG and RANKL may also originate from non-skeletal sources. Thirdly, the commercially available assays were designed to detect all forms of OPG (monomer, dimer, RANKL/OPG complex) and not exclusively the dimeric form, which is thought to be the biologically active form [41]. Fourthly, serum RANKL constitutes only a small part of total RANKL, as the majority is cell bound and thus not detectable in the circulation.…”

“…Fourthly, serum RANKL constitutes only a small part of total RANKL, as the majority is cell bound and thus not detectable in the circulation. However, a more accurate method that assesses cell-surface production of RANKL is very impractical in humans [41] because it requires bone biopsy.…”

Levels of osteoprotegerin (OPG) and receptor activator for nuclear factor kappa B ligand (RANKL) in serum: Are they of any help?

“…These results indicate that hPTH initially stimulates osteoblast maturation and function, which in turn leads to osteoclast activation and a gradual rebalancing of bone formation and resorption [57,58]. Again, results remain conflicting as a themenschwerpunkt small uncontrolled study described a decrease of RANKL and unchanged OPG levels, under not only teriparatide but also risedronate therapy [59].…”

Relationship between serum RANKL and RANKL in bone

“…For example, serum RANKL was found to increase in multiple myeloma and to predict survival in this disease [36] and low serum RANKL was found to be a predictor of fragility fracture [37]. In terms of treatment, anabolic therapy with PTH resulted in a rapid (within 1 h) increase in serum RANKL (with no change in OPG levels), which was sustained for at least 1 month [38], whereas risedronate treatment resulted in decreased serum RANKL levels, with a small increase in OPG levels [39].…”