Effects of denosumab on bone turnover markers in postmenopausal osteoporosis

• Published in: Journal of bone and mineral research Vol. 26; no. 3; pp. 530 - 537
• Main Authors: Eastell, Richard, Christiansen, Claus, Grauer, Andreas, Kutilek, Stepan, Libanati, Cesar, McClung, Michael R, Reid, Ian R, Resch, Heinrich, Siris, Ethel, Uebelhart, Daniel, Wang, Andrea, Weryha, Georges, Cummings, Steve R
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.03.2011; Wiley; Oxford University Press
• Subjects: Acid Phosphatase - blood; Aged; Aged, 80 and over; Alkaline Phosphatase - blood; Antibodies, Monoclonal - pharmacology; Antibodies, Monoclonal - therapeutic use; Antibodies, Monoclonal, Humanized; Biological and medical sciences; Biomarkers - blood; BONE ALKALINE PHOSPHTASE (BALP); Bone Density - drug effects; Bone Density Conservation Agents - pharmacology; Bone Density Conservation Agents - therapeutic use; Bone Remodeling - drug effects; BONE TURNOVER MARKERS; Collagen Type I - blood; C‐TELOPEPTIDE OF TYPE I COLLAGEN (CTX); DENOSUMAB; Dose-Response Relationship, Drug; Female; Fundamental and applied biological sciences. Psychology; Humans; Isoenzymes - blood; Middle Aged; OSTEOPOROSIS; Osteoporosis, Postmenopausal - blood; Osteoporosis, Postmenopausal - drug therapy; Osteoporosis, Postmenopausal - enzymology; Osteoporosis, Postmenopausal - physiopathology; Peptide Fragments - blood; Peptides - blood; Procollagen - blood; PROCOLLAGEN TYPE I N‐TERMINAL PROPEPTIDE (PINP); RANK Ligand - pharmacology; RANK Ligand - therapeutic use; Reference Values; Skeleton and joints; Statistics, Nonparametric; Tartrate-Resistant Acid Phosphatase; TARTRATE‐RESISTANT ACID PHOSPHATASE (TRACP 5b); Vertebrates: osteoarticular system, musculoskeletal system; Procollagen; Enzyme; Diseases of the osteoarticular system; Phosphoric monoester hydrolases; Esterases; BONE ALKALINE PHOSPHTASE (BALP); Monoclonal antibody; Denosumab; TARTRATE-RESISTANT ACID PHOSPHATASE (TRACP 5b); Osteoarticular system; Tartrate; Osteoporosis; Vertebrata; C-TELOPEPTIDE OF TYPE I COLLAGEN (CTX); Mammalia; Collagen type I; N terminal-Sequence; Turnover; Postmenopause; Hydrolases; PROCOLLAGEN TYPE I N-TERMINAL PROPEPTIDE (PINP); Bone; Acid phosphatase; BONE TURNOVER MARKERS
• ISSN: 0884-0431; 1523-4681; 1523-4681
• DOI: 10.1002/jbmr.251

Denosumab, a fully human monoclonal antibody to RANKL, decreases bone remodeling, increases bone density, and reduces fracture risk. This study evaluates the time course and determinants of bone turnover marker (BTM) response during denosumab treatment, the percentage of denosumab‐treated women with BTMs below the premenopausal reference interval, and the correlations between changes in BTMs and bone mineral density (BMD). The BTM substudy of the Fracture REduction Evaulation of Denosumab in Osteoporosis every 6 Months (FREEDOM) Trial included 160 women randomized to subcutaneous denosumab (60 mg) or placebo injections every 6 months for 3 years. Biochemical markers of bone resorption (serum C‐telopeptide of type I collagen [CTX] and tartrate‐resistant acid phosphatise [TRACP‐5b]) and bone formation (serum procollagen type I N‐terminal propeptide [PINP] and bone alkaline phosphatase [BALP]) were measured at baseline and at 1, 6, 12, 24, and 36 months. Decreases in CTX were more rapid and greater than decreases in PINP and BALP. One month after injection, CTX levels in all denosumab‐treated subjects decreased to levels below the premenopausal reference interval. CTX values at the end of the dosing period were influenced by baseline CTX values and the dosing interval. The percentage of subjects with CTX below the premenopausal reference interval before each subsequent injection decreased from 79% to 51% during the study. CTX and PINP remained below the premenopausal reference interval at all time points in 46% and 31% denosumab‐treated subjects, respectively. With denosumab, but not placebo, there were significant correlations between CTX reduction and BMD increase (r = −0.24 to −0.44). The BTM response pattern with denosumab is unique and should be appreciated by physicians to monitor this treatment effectively. © 2011 American Society for Bone and Mineral Research.