Bone strength

The acellular structure of real bone is modified continuously according to the internal stresses caused by applied loads. This process, which represents an attempt to optimize the strength-to-weight ratio in a biological structure, is achieved by the interaction between two types of cell, one that absorbs bone and the other that synthesises new bone. New bone is added where internal stresses are high, and bone is removed where stresses are low. An accurate finite-element model of this combined process could be used clinically to determine the course of traction that will maximise bone strength after recovery from a fracture. 

Picherit et al., 2000 1 yr old OVX rats oral administration, 90 d genistein or daidzein at 10 mg/kg body weight Overall daidzein > genistein in this study. Total femoral BMD losses and vertebral trabecular bone were protected by estradiol and daidzein, but genistein was not efficient. Bone strength (femoral failure stress) protected by estradiol, daidzein and genistein... 

OMi N, AOi s, MURATA K and EZAWA I (1992) Evaluation of the effect of soybean milk and soybean milk peptide on bone metabolism in the rat model with bone strength in ovariectomized osteoporotic rats. JNutr Sci Vitaminol 40, 201-1E... 

The human skeleton consists of both cortical and trabecular bone. Cortical bone is dense and compact and is responsible for much of bone strength. It is the most common type of... 

Osteoporosis is a skeletal disorder characterized by compromised bone strength predisposing individuals to an increased fracture risk. 

Ammann P, Bourrin S, Bonjour J-P, Brunner F, Meyer J-M, Rizzoli R (1999) The new selective estrogen receptor modulator MDL 103, 323 increases bone mineral density and bone strength in adult ovariectomized rats. Osteoporos Int 10 369-376... 

Ke HZ, Qi H, Chidsey-Frink KL, Crawford DT, Thompson DD (2001) Lasofoxifene (CP-336,156) protects against the age-related changes in bone mass, bone strength, and total serum cholesterol in intact aged male rats. J Bone Miner Res 16 765-773... 

Ke HZ, Foley GL, Simmons HA, Shen V, Thompson DD (2004) Long-term treatment of lasofoxifene preserves bone mass and bone strength and does not adversely affect the uterus in ovariectomized rats. Endocrinology 145 1996-2005... 

Osteoporosis is currently defined as a skeletal disorder characterized by compromised bone strength predisposing to an increased risk of fracture. Bone strength reflects the integration of two main features bone density and bone quality (NIH Consensus 2001). Thus, osteoporosis is a debilitating condition of the skeleton that propends to fractures and is associated with advanced age. The disease has a high prevalence in western countries, as it is a condition associated with advanced age, and it is on the rise since fife expectancy has risen dramatically in the last several decades. It is, therefore, a major public health problem because it not only induces morbidity (fractures and chronic sequelae) with a substantial impact on health-related quality of life, but is also associated with increased mortality (Badia et al. 2001, 2004). 

Lasofoxifene is a SERM that also protects from bone loss, reduces cholesterol levels, and exerts a positive effect on bone strength in rats, specifically in male models (Ma et al. 2002). This compound is in the final stages of clinical development. Two other SERMs also in advanced phase III trials are bazedoxifene and arzoxifene, both with protective effects against ovariectomy-induced bone loss. Arzoxifene has shown both bone remodeling reduction with positive effects on bone quality as well as a reduction in cholesterol levels in oophorectomized rats (Biskobing2003). 

From these data one can conclude that antiresorptives are capable of inducing striking reductions in fracture risk with limited changes in bone density. Therefore, other factors than bone density should explain their efficacy. Bone quality is the term that encompasses all the non-bone-density elements implied in bone strength, as previously discussed. 

Burr DB (2003) Microdamage and bone strength. Osteoporos Int 14(Suppl 5) 67-72... 

Bone strength however declines much earlier in life beginning approximately age 20 for both men and women (8j. In animals bone strength is directly related with its mineral content (9-12). 

Based on limited epidemiologic evidence, fluoride supplements, with or without calcium, estrogen and vitamin D, are used by clinicians for the treatment of osteoporosis. However, knowledge of the effects of fluoride on calcium and phosphorus metabolism in normal animals is limited although Spencer et al. (32) reported that ingestion of fluoride by three osteoporotic men did not affect calcium absorption but caused a decrease in urinary excretion. Moreover, there is a need to determine the long-term effects of fluoride treatment on bone strength and on soft tissues ( ). 

EPO is used in blood doping to generate more red blood cells for carrying oxygen. It is particularly favored by endurance athletes to enhance their performance. Human growth hormone (hGH, see description in Section 4.5.2) is used to build up muscle and bone strength. Both EPO and hGH are banned in sports. 

Osteoporosis is a serious matter. Cells known as osteoblasts make bone cells known as osteoclasts degrade bone. It may not be obvious but the action of osteoclasts is important. We do small amounts of damage to our bones in the course of our daily activities. These damaged areas need to be repaired to ensure continued bone strength. The osteoclasts remove the small areas of damaged bone and the osteoblasts fill in the gap with new bone. The damage is repaired and bone strength maintained. 

C.H. Turner, L.P. Garetto, A.J. Dunipace, W. Zhang, M.E. Wilson, M.D. Grynpas, D. Chachra, R. McClintock, M. Peacock, G.K. Stookey, Fluoride treatment increased serum IGF-1, bone turnover, but not bone strength, in rabbits, Calcif. Tissue Int. 61 (1997) 77-83. 

Chapin, R.E., W.W. Ku, M.A. Kenney, and H. McCoy. 1998. The effects of dietary boric acid on bone strength in rats. Biol. Trace Elem. Res. 66 395-399. 

Calcium is also found in the rigid structural components of living things, either as the calcium carbonate of the shells of shellfish or the calcium phosphate of bone. About a kilogram of calcium is present in an adult human body, mostly in the form of insoluble calcium phosphate, but also as Ca2T ions in other fluids inside our cells. The calcium in newly formed bone is in dynamic equilibrium with the calcium ions in the body fluids, so calcium must be part of our daily diet to maintain bone strength. 

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