Variations in nanomechanical properties and tissue composition within trabeculae from an ovine model of osteoporosis and treatment

• Published in: Bone (New York, N.Y.) N.Y.), 2013-01, Vol.52 (1), p.326-336
• Main Authors: Burket, Jayme C, Brooks, Daniel J, MacLeay, Jennifer M, Baker, Shefford P, Boskey, Adele L, van der Meulen, Marjolein C.H
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Biomechanical Phenomena; Bisphosphonate; Bone (cancellous); Bone composition; Bone Density Conservation Agents - therapeutic use; Bone mineral density; Bones, joints and connective tissue. Antiinflammatory agents; Cancellous bone; carbonates; Collagen; Composition; Crystallinity; Diphosphonates - therapeutic use; Disease Models, Animal; Diseases of the osteoarticular system; Drugs; Estrogen receptors; Fractures; Fundamental and applied biological sciences. Psychology; Imidazoles - therapeutic use; Mechanical properties; Medical sciences; Mineralization; Nanomechanical properties; Nanotechnology; Orthopedics; Osteoporosis; Osteoporosis - drug therapy; Osteoporosis - physiopathology; Osteoporosis. Osteomalacia. Paget disease; Pharmacology. Drug treatments; Raloxifene; Raloxifene Hydrochloride - therapeutic use; Risk assessment; SERM; Sheep; Spatial distribution; Spectrum Analysis, Raman; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Zoledronic acid
• ISSN: 8756-3282; 1873-2763
• DOI: 10.1016/j.bone.2012.10.018

Abstract Osteoporosis and treatment may affect both composition and nanomechanical properties and their spatial distributions within the individual trabeculae of cancellous bone at length scales that cannot be captured by bulk measurements. This study utilized 25 mature adult ewes divided into 5 treatment groups. Four treatment groups were given a dietary model for human high-turnover osteoporosis, and two of these were treated with antiresorptive drugs, either zoledronate (ZOL) or raloxifene (RAL), to examine their effects on bulk tissue properties and nanoscale tissue composition and mechanical properties within trabeculae. Treatment effects were most pronounced at the nanoscale, where RAL increased indentation modulus and hardness throughout trabeculae by 10% relative to the osteoporosis model. In comparison, ZOL increased these properties exclusively at the surfaces of trabeculae (indentation modulus + 12%, hardness + 16%). Nanomechanical alterations correlated with changes in tissue mineralization, carbonate substitution, crystallinity, and aligned collagen. Despite only minimal changes in bulk tissue tBMD, the nanomechanical improvements within trabeculae with both treatments greatly improved the predicted theoretical bending stiffness of individual trabeculae when idealized as cylindrical struts. Hence, small tissue-level alterations in critical locations for resisting trabecular failure could account for some of the discrepancy between the large reductions in fracture risk and the only modest changes in BMD with antiresorptive treatments.