Effect of Increased 25(OH)D on Bone Health, a High Resolution Peripheral Computed Tomography Study

Vitamin D is important for normal bone health, however, there is still debate over the intake for optimal bone health. The objective of this study is to assess the relationship between large changes in 25(OH)D to bone health, and the safety of taking up to 10,000 IU/day of vitamin D over one-year using a pilot cohort of a three-year ongoing randomized control trial. The results suggest that with increased 25(OH)D there was an improvement in trabecular and cortical BMD, as well as a decrease in cortical area and thickness, while maintaining bone strength. Based on biomarker data, taking doses of vitamin D up to 10,000 IU/day for one year was found to be safe within the population studied. This study has provided new insight into the understanding of large changes in 25(OH)D on bone health and demonstrates the importance of 25(OH)D for maintaining bone health in a healthy adult population.

Year	Entry
1997	Kanis JA, Delmas P, Burckhardt P, Cooper C, Torgerson D; European Foundation for Osteoporosis and Bone Disease. Guidelines for diagnosis and management of osteoporosis. Osteoporos Int. July 1997;7(4):390-406.
2011	Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, Weaver CM. Evaluation, treatment, and prevention of vitamin D deficiency: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. July 2011;96(7):1911-1930.
2007	MacNeil JA, Boyd SK. Accuracy of high-resolution peripheral quantitative computed tomography for measurement of bone quality. Med Eng Phys. December 2007;29(10):1096-1105.
2008	MacNeil JA, Boyd SK. Bone strength at the distal radius can be estimated from high-resolution peripheral quantitative computed tomography and the finite element method. Bone. June 2008;42(6):1203-1213.
2002	Pistoia W, van Rietbergen B, Lochmüller E-M, Lill CA, Eckstein F, Rüegsegger P. Estimation of distal radius failure load with micro-finite element analysis models based on three-dimensional peripheral quantitative computed tomography images. Bone. June 2002;30(6):842-848.
2002	Kontulainen S, Sievänen H, Kannus P, Pasanen M, Vuori I. Effect of long‐term impact‐loading on mass, size, and estimated strength of humerus and radius of female racquet‐sports players: a peripheral quantitative computed tomography study between young and old starters and controls. J Bone Miner Res. December 2002;17(12):2281-2289.
1996	Garnero P, Hausherr E, Chapuy M, Marcelli C, Grandjean H, Muller C, Cormier C, Bréart G, Meunier PJ, Delmas PD. Markers of bone resorption predict hip fracture in elderly women: the EPIDOS prospective study. J Bone Miner Res. October 1996;11(10):1531-1538.
2016	Shanbhogue VV, Brixen K, Hansen S. Age- and sex-related changes in bone microarchitecture and estimated strength: a three-year prospective study using HRpQCT. J Bone Miner Res. August 2016;31(8):1541-1549.
2005	Boutroy S, Bouxsein ML, Munoz F, Delmas PD. In vivo assessment of trabecular bone microarchitecture by high-resolution peripheral quantitative computed tomography. J Clin Endocrinol Metab. December 2005;90(12):6508-6515.
2008	Clarke B. Normal bone anatomy and physiology. Clin J Am Soc Nephrol. November 2008;3(suppl 3):S131-S139.
2010	Burghardt AJ, Buie HR, Laib A, Majumdar S, Boyd SK. Reproducibility of direct quantitative measures of cortical bone microarchitecture of the distal radius and tibia by HR-pQCT. Bone. September 2010;47(3):519-528.
2014	Ellouz R, Chapurlat R, van Rietbergen B, Christen P, Pialat J-B, Boutroy S. Challenges in longitudinal measurements with HR-pQCT: evaluation of a 3D registration method to improve bone microarchitecture and strength measurement reproducibility. Bone. June 2014;63:147-157.
2016	Weaver CM, Gordon CM, Janz KF, Kalkwarf HJ, Lappe JM, Lewis R, O’Karma M, Wallace TC, Zemel BS. The National Osteoporosis Foundation’s position statement on peak bone mass development and lifestyle factors: a systematic review and implementation recommendations. Osteoporos Int. April 2016;27(4):1281-1386.
2011	Macdonald HM, Nishiyama KK, Kang J, Hanley DA, Boyd SK. Age‐related patterns of trabecular and cortical bone loss differ between sexes and skeletal sites: a population‐based HT‐pQCT study. J Bone Miner Res. January 2011;26(1):50-62.
1999	Laib A, Rüegsegger P. Comparison of structure extraction methods for in vivo trabecular bone measurements. Comput Vis Image Understand. March–April 1999;23(2):69-74.
2014	Kawalilak CE, Johnston JD, Olszynski WP, Kontulainen SA. Characterizing microarchitectural changes at the distal radius and tibia in postmenopausal women using HR-pQCT. Osteoporos Int. August 2014;25(8):2057-2066.
2000	Garner P, Sornay-Rendu E, Claustrat B, Delmas PD. Biochemical markers of bone turnover, endogenous hormones and the risk of fractures in postmenopausal women: the OFELY study. J Bone Miner Res. August 2000;15(8):1526-1536.
1988	Recker RR, Kimmel DB, Parfitt MA, Davies MK, Keshawarz N, Hinders S. Static and tetracycline‐based bone histomorphometric data from 34 normal postmenopausal females. J Bone Miner Res. April 1988;3(2):133-344.
2015	Manske SL, Zhu Y, Sandino C, Boyd SK. Human trabecular bone microarchitecture can be assessed independently of density with second generation HR-pQCT. Bone. October 2015;79:213-221.
2007	Buie HR, Campbell GM, Klinck RJ, MacNeil JA, Boyd SK. Automatic segmentation of cortical and trabecular compartments based on a dual threshold technique for in vivo micro-CT bone analysis. Bone. October 2007;41(4):505-515.
2007	Blake GM, Fogelman I. The role of DXA bone density scans in the diagnosis and treatment of osteoporosis. Postgrad Med J. August 2007;83(982):509-517.
1995	van Rietbergen B, Weinans H, Huiskes R, Odgaard A. A new method to determine trabecular bone elastic properties and loading using micromechanical finite-element models. J Biomech. January 1995;28(1):69-81.
2002	Boyd SK, Müller R, Zernicke RF. Mechanical and architectural bone adaptation in early stage experimental osteoarthritis. J Bone Miner Res. April 2002;17(4):687-694.
2012	Pauchard Y, Liphardt A-M, Macdonald HM, Hanley DA, Boyd SK. Quality control for bone quality parameters affected by subject motion in high-resolution peripheral quantitative computed tomography. Bone. June 2012;50(6):1304-1310.
2011	Vasikaran S, Eastell R, Bruyère O, Foldes AJ, Garnero P, Griesmacher A, McClung M, Morris HA, Silverman S, Trenti T, Wahl DA, Cooper C, Kanis JA; OF-IFCC Bone Marker Standards Working Group. Markers of bone turnover for the prediction of fracture risk and monitoring of osteoporosis treatment: a need for international reference standards. Osteoporos Int. February 2011;22(2):391-420.
2006	Hadjidakis DJ, Androulakis II. Bone remodeling. Annals NY Acad Sci. December 2006;1092(1):385-396.
2010	Eriksen EF. Cellular mechanisms of bone remodeling. Rev Endocr Metab Disord. December 2010;11(4):219-227.
2006	Szulc P, Seeman E, Duboeuf F, Sornay-Rendu E, Delmas PD. Bone fragility: failure of periosteal apposition to compensate for increased endocortical resorption in postmenopausal women. J Bone Miner Res. December 2006;21(12):1856-1863.
2000	Manolagas SC. Birth and death of bone cells: basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis. Endocr Rev. April 2000;21(2):115-137.

Year

Entry

1997

Kanis JA, Delmas P, Burckhardt P, Cooper C, Torgerson D; European Foundation for Osteoporosis and Bone Disease. Guidelines for diagnosis and management of osteoporosis. Osteoporos Int. July 1997;7(4):390-406.

2011

Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, Weaver CM. Evaluation, treatment, and prevention of vitamin D deficiency: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. July 2011;96(7):1911-1930.

2007

MacNeil JA, Boyd SK. Accuracy of high-resolution peripheral quantitative computed tomography for measurement of bone quality. Med Eng Phys. December 2007;29(10):1096-1105.

2008

MacNeil JA, Boyd SK. Bone strength at the distal radius can be estimated from high-resolution peripheral quantitative computed tomography and the finite element method. Bone. June 2008;42(6):1203-1213.

2002

Pistoia W, van Rietbergen B, Lochmüller E-M, Lill CA, Eckstein F, Rüegsegger P. Estimation of distal radius failure load with micro-finite element analysis models based on three-dimensional peripheral quantitative computed tomography images. Bone. June 2002;30(6):842-848.