Is the paradigm shifting?

Reduction in bone mass has long dominated the thinking about and approach to the problem of osteoporosis. A now large body of evidence indicates that bone mass is not adequate to explain satisfactorily either the skeletal fragility of osteoporosis or the effects of bone active agents. By contrast, bone remodeling activity seems to provide a better explanation of both. It is suggested that current syntheses in the field are shifting to this conclusion. In attempting to make sense out of how a process designed by evolution to sustain bone strength could instead be contributing to weakness, I suggest: (1) prevailing bone remodeling levels are substantially higher than are optimal for maintenance of bone strength; (2) this high level has discernible environmental causes; and (3) such high remodeling is a major source-perhaps the major source-of osteoporotic bony fragility. Within this context, reduced bone mass, rather than the primary cause of fracture, is seen as a factor that predisposes individuals to the harmful effects of excessive remodeling.

[1]  P. Ross,et al.  Serum Bone Alkaline Phosphatase and Calcaneus Bone Density Predict Fractures: A Prospective Study , 2000, Osteoporosis International.

[2]  R. Lindsay,et al.  Resistance to Bone Resorbing Effects of PTH in Black Women , 1997, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[3]  H. Kopera,et al.  Briefe an die Redaktion , 1989, Klinische Wochenschrift.

[4]  B. L. Riggs,et al.  Bone Turnover Matters: The Raloxifene Treatment Paradox of Dramatic Decreases in Vertebral Fractures Without Commensurate Increases in Bone Density , 2002, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[5]  W. O'Fallon,et al.  Primary Hyperparathyroidism and the Risk of Fracture: A Population‐Based Study , 1999, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[6]  L. Joseph Melton,et al.  Perspective how many women have osteoporosis? , 1992, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[7]  J. Aloia,et al.  Biochemical and hormonal variables in black and white women matched for age and weight. , 1998, The Journal of laboratory and clinical medicine.

[8]  M. Holick,et al.  Nutrition and Bone Health , 2004, Nutrition and Health.

[9]  M. McClung Therapy for fracture prevention. , 1999, JAMA.

[10]  J Pearson,et al.  Prevalent Vertebral Deformities Predict Hip Fractures and New Vertebral Deformities but Not Wrist Fractures , 1999, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[11]  R. Eastell,et al.  Relationship of Early Changes in Bone Resorption to the Reduction in Fracture Risk With Risedronate , 2003, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[12]  G. Blake,et al.  Quantitative studies of bone in postmenopausal women using (18)F-fluoride and (99m)Tc-methylene diphosphonate. , 2002, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[13]  O. Johnell,et al.  Additive effects of raloxifene and alendronate on bone density and biochemical markers of bone remodeling in postmenopausal women with osteoporosis. , 2002, The Journal of clinical endocrinology and metabolism.

[14]  M S Calvo,et al.  Prevalence of Low Femoral Bone Density in Older U.S. Adults from NHANES III , 1997, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[15]  A. Vesterby,et al.  Bone histomorphometry in hypoparathyroid patients treated with vitamin D. , 1996, Bone.

[16]  R. Epstein,et al.  Pre-existing fractures and bone mass predict vertebral fracture incidence in women. , 1991, Annals of internal medicine.

[17]  A. Parfitt High Bone Turnover Is Intrinsically Harmful: Two Paths to a Similar Conclusion: The Parfitt View , 2002, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[18]  Claus Christiansen,et al.  Consensus development conference: Prophylaxis and treatment of osteoporosis , 2005, Osteoporosis International.

[19]  D. Black,et al.  Relationships Between Bone Mineral Density and Incident Vertebral Fracture Risk with Raloxifene Therapy , 2002, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[20]  C. Christiansen,et al.  Six and Twelve Month Changes in Bone Turnover are Related to Reduction in Vertebral Fracture Risk During 3 Years of Raloxifene Treatment in Postmenopausal Osteoporosis , 2001, Osteoporosis International.

[21]  H. Oxlund,et al.  Reduced concentration of collagen reducible cross links in human trabecular bone with respect to age and osteoporosis. , 1996, Bone.

[22]  C. Slemenda,et al.  Age and bone mass as predictors of fracture in a prospective study. , 1988, The Journal of clinical investigation.

[23]  M. Hochberg,et al.  Changes in bone density and turnover explain the reductions in incidence of nonvertebral fractures that occur during treatment with antiresorptive agents. , 2002, The Journal of clinical endocrinology and metabolism.

[24]  D. Burr,et al.  Dynamic bone remodeling in later Pleistocene fossil hominids. , 1996, American journal of physical anthropology.

[25]  C. Weaver,et al.  Changes in calcium kinetics in adolescent girls induced by high calcium intake. , 2000, The Journal of clinical endocrinology and metabolism.

[26]  Fran Harris,et al.  Improvement in spine bone density and reduction in risk of vertebral fractures during treatment with antiresorptive drugs. , 2002, The American journal of medicine.

[27]  I. Chiodini,et al.  Different patterns of global and regional skeletal uptake of 99mTc-methylene diphosphonate with age: relevance to the pathogenesis of bone loss. , 2000, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[28]  C. Erem,et al.  RELATIONSHIP OF BONE TURNOVER PARAMETERS, ENDOGENOUS HORMONES AND VIT D DEFICIENCY TO HIP FRACTURE IN ELDERLY POSTMENOPAUSAL WOMEN , 2002, International journal of clinical practice.

[29]  S. New Nutrition Society Medal Lecture: The role of the skeleton in acid—base homeostasis , 2002, Proceedings of the Nutrition Society.

[30]  C. Cooper,et al.  Perspective how many women have osteoporosis? , 1992, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[31]  T. Kuhn,et al.  The Structure of Scientific Revolutions. , 1964 .

[32]  D. Meier,et al.  Calcium, vitamin D, and parathyroid hormone status in young white and black women: association with racial differences in bone mass. , 1991, The Journal of clinical endocrinology and metabolism.

[33]  L. Melton,et al.  Drug therapy for vertebral fractures in osteoporosis: evidence that decreases in bone turnover and increases in bone mass both determine antifracture efficacy. , 1996, Bone.

[34]  M. Burritt,et al.  Role of calcium intake in modulating age-related increases in parathyroid function and bone resorption. , 1996, The Journal of clinical endocrinology and metabolism.

[35]  C Marcelli,et al.  Markers of bone resorption predict hip fracture in elderly women: The EPIDOS prospective study , 1996, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[36]  O. Johnell,et al.  Biochemical Indices of Bone Turnover and the Assessment of Fracture Probability , 2002, Osteoporosis International.

[37]  P. Meunier,et al.  Alendronate increases bone strength by increasing the mean degree of mineralization of bone tissue in osteoporotic women. , 2000, Bone.

[38]  D. Nelson,et al.  Calcium in evolutionary perspective. , 1991, The American journal of clinical nutrition.

[39]  P. Garnero Markers of Bone Turnover for the Prediction of Fracture Risk , 2000, Osteoporosis International.

[40]  R. Heaney,et al.  Bisphosphonate Effects and the Bone Remodeling Transient , 1997, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[41]  P. Delmas,et al.  Markers of Bone Turnover Predict Postmenopausal Forearm Bone Loss Over 4 Years: The OFELY Study , 1999, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[42]  Claus Christiansen,et al.  Diagnosis of Osteoporosis , 1992, Southern medical journal.

[43]  W. O'Fallon,et al.  Relationship of Bone Turnover to Bone Density and Fractures , 1997, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.