Comparative responses of bone turnover markers to bisphosphonate therapy in Paget's disease of bone

• Published in: Bone (New York, N.Y.) N.Y.), 2004-07, Vol.35 (1), p.224-230
• Main Authors: Reid, Ian R, Davidson, James S, Wattie, Diana, Wu, Fiona, Lucas, Jenny, Gamble, Gregory D, Rutland, Michael D, Cundy, Tim
• Format: Article
• Language: English
• Subjects: Aged; Biological and medical sciences; Biomarkers - analysis; Bisphosphonates; Bone Remodeling - drug effects; Bone turnover markers; Diphosphonates - therapeutic use; Diseases of the osteoarticular system; Female; Fundamental and applied biological sciences. Psychology; Humans; Male; Medical sciences; Middle Aged; Osteitis Deformans - drug therapy; Osteitis Deformans - metabolism; Osteoporosis. Osteomalacia. Paget disease; Paget's disease; Randomized Controlled Trials as Topic; Traumas. Diseases due to physical agents; Vertebrates: anatomy and physiology, studies on body, several organs or systems
• ISSN: 8756-3282; 1873-2763
• DOI: 10.1016/j.bone.2004.03.023

The measurement of biochemical markers of bone turnover is integral to the diagnosis and management of Paget's disease. Recently, there has been a proliferation of new markers and a move to carry out existing assays on automated platforms. We have assessed the performance of seven currently available markers in 20 patients with Paget's disease undergoing ibandronate therapy (6 or 12 mg) and in nine placebo-treated controls. Samples were collected at baseline and 6 months following intervention. The mean reductions in serum markers following treatment with either dose of ibandronate were: total alkaline phosphatase (AP; Roche Modular) 70%, bone AP (Beckman Access, Ostase) 80%, osteocalcin (Roche Elecsys 2010) 33%, β-C-terminal telopeptide of type I collagen (βCTX; Roche Elecsys 2010) 50%, and procollagen-N-terminal peptide (P1NP; Roche Elecsys 2010) 80%. For urine markers the reductions were: free deoxypyridinoline/creatinine (fDPD/creat) (DPC Immulite 2000) 36%, and N-telopeptide/creatinine (NTX/creat) (Osteomark) 81%. Total AP, bone AP, P1NP, and NTX all showed >95% of subjects to have abnormal values at baseline, reducing to 15–30% following treatment, and these treatment effects were highly significant ( P ≤ 0.0005), except for NTX ( P = 0.02). The poorer precision of NTX reduced its utility. Baseline sensitivity was lower for the other markers (osteocalcin 68% of subjects abnormal, fDPD 22%, βCTX 50%). Total AP, bone AP, and P1NP are suitable osteoblast markers for monitoring bisphosphonate therapy in Paget's disease, with performance approaching that of bone scintigraphy. NTX is less sensitive in detecting the effects of therapy, but is the best performing bone resorption marker. There is no clear evidence from this study that any of these newer markers are superior to total AP in assessing patients with this severity of Paget's disease.