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Bone quality, strength and stiffness

Written by Amy
Tuesday, 27 September 2005

From "Bone Quality: What is it and how can we measure it?" Meeting in Maryland, Bethesda May 2005

Amy Hoang-Kim

"One in three women and one in eight men over the age of 50" suffer typically from osteoporosis. An osteoporotic or fragility fracture is caused by a deterioration of microstructure in healthy bone due to low bone mineral density (BMD) followed by a fall or similar minor trauma.

Explaining the occurrence of such fragility fractures have precipitated scientists, surgeons and physicians into definitions and terminology related to "bone density". Bone quality, bone mineral content, bone mineral density, bone mineral apparent density, bone strength and bone fragility have all gained equal status in recent research. We can only begin to wade through the conundrum of terms to see if we truly understand underlying mechanisms.

• Bone Quality – defined by at least four factors: (1) the rate of bone turnover (2) properties of the collagen/mineral matrix (3) microdamage accumulation; (4) architecture/geometry of cancellous and cortical bone [1]
• Bone Mineral Content – BMC measures the total amount of bone in a given region and is dependent on the size of the region in question. Recent literature on women with scoliosis and osteoporosis has reported adaptive responses in both BMD and BMC to prevailing mechanical loads. Percent change in BMC depended on the applied moment and the local curvature. The same dependence was observed for the percent change in BMD, but in this case, the shear force was also significantly inversely correlated [2].
• Bone Mineral Density -- is an average of the pixel density throughout an area of the scan identified by the scanner software as representing bone. The term is often clarified as areal BMD whereas, bone mineral apparent density and vBMD adjust for body size or attempts to approximate a true volumetric density value. Therefore, in actual fact, BMD is a 2-D surrogate for 3-D volume. The mathematical explanation resides in the following equation: aBMD = BMC / area [3].
• Bone Strength – is the relative ability of a skeletal structure to sustain the loads it is likely to experience in everyday life without fracturing. Here, strength is directly proportional to both bone mass and bone size.
• Bone loss – A loss of one standard deviation gives rise to an enhanced two-fold risk of spine fractures or a 2.5 risk of hip fracture [4].

These interrelationships seldom have been examined particularly across different skeletal sites. While it is also important to realize the technological limitations of testing true bone density, (the mass of bone per unit volume of bone—exclusive of marrow and other non-bone tissue) dual energy x-ray absorptiometry (DXA) scanners remain, for practical reasons, the best diagnostic tool in a clinical setting.

EFFECTS OF MICRODAMAGE ON BONE STRENGTH

It is essential that we examine factors related to fragility fractures that are also independent from BMD measurements. Microdamage accumulates with age and is directly related to the reduction of bone strength, stiffness and toughness according to D. Burr [5]. The collagen-mineral property of bone acts as an agent in itself in preventing the propagation of cracks and crack growth. Ultimately, this process is retarded with age because of the excess in mineralization apparent in the bone at this stage of life. In essence, the bone becomes more homogenous and there are fewer “stress discontinuities” which are areas where active crack-bridging generally occur. There are still many unresolved issues concerning pharmaceutical agents and their ability to increase bone mineralization regardless of the diminishing stiffness heterogeneity in the tissue, which contributes of course to overall bone strength. In other words, what is more important-- increasing bone mineralization or reducing bone homogeneity? [6]

CLINICAL RELEVANCE OF MICRODAMAGE ACCUMULATION AND EXCESS REMODELING SUPPRESSION

The restorative bone remodeling process has a tendency to gravitate towards areas of micro-damage [7]. Dr. Recker states that “Surely, mechanically-driven bone remodeling weakens bone transiently [4]. But it is more than compensated for by the gain in strength resulting from removal of micro-damage”. Thus, the suppression of bone remodeling by as much as 60-70% accounts for more than half of the anti-fracture effect of treatment with bisphosphonates. There are evident mechanisms which take place in order to improve bone quality: 1) elimination or reduction in trabecular penetration and trabecular loss which preserves connectivity; 2) reduction in trabecular and cortical thinning; and 3) reduction in the fraction of newly formed, undermineralized osteoid. Interestingly, when the amount of newly-formed bone supersedes the biological need required for skeletal repair, there is in actual fact, up to 50-60% weakening of bone quality [8]. Dr. Recker further notes however, that an average 60-70% reduction in remodeling rates in osteoporosis patients results in rates comparable to healthy, non-fracturing pre-menopausal women [9]. What is apparent is the need for further investigation on other elements intrinsic to bone remodeling that may cause inappropriate low-trauma fractures.

COMPREHENSIVE SKELETAL PHENOTYPING TO ASSESS BONE QUALITY

Genetic mapping dealing with the aforementioned parameters is necessary to find out whether these phenotypes are important in osteoporotic fractures. In a study by Henderson et al [10], recombinant congenic strains of mice were used to identify genes that confer susceptibility or resistance to osteoporosis. The authors found BMD less reliable than quanititative CT for initial identification of bone phenol-deviants; qCT correlates with histomorphometric and biochemical indices of bone turnover and finally, trabecular and cortical bone are regulated by different genetic mechanisms. A second study by van Lenthe et al. [11] investigated the genetics of femoral neck strength. An F2 population of 2,000 mice was used to analyze femora and L5-vertebra, to assess specific genetic influence on cortical and trabecular bone, and to determine the associated genetic loci. The use of a micro-computed tomography-based finite-element(µFE) enabled identification of genetic loci directly for bone strength. It was also shown that genetic variability in bone brittleness is established early in life as reported by Price et al. [12]. In the 3 inbred strains, the authors quantified femoral morphology and composition throughout life. Each strain showed a non-linear increase in ash content between 14 and 112 days of age. The tissue of murine femurs of strain C57B/6J had lower material stiffness, but greater ductility throughout life and differences in material quality among the strains could be observed prior to 14 days of age. Furthermore, recombinant Inbred (RI) strains have a unique pattern of genetic randomization that can be used to measure the tendency of different traits to cosegregate. According to K. Jepsen [13], the networks derived from these mice possess higher-level biological controls. Genetic research can not negate the challenge posed by genetic mutations or pharmacological treatments in studying biological traits.

References:

1. Burr, DB. Bone Quality: Understanding what matters. J Musculoskel Neuron Interact 2004; 4 (2): 184-186
2. Routh, R, Rumancik, S, Pathak R, Burshell A, Nauman E. The relationship between bone mineral density and biomechanics in patients with osteoporosis and scoliosis. Osteoporosis International online first. 2005; 10.007/s00198-005-1951-z
3. Heaney R. BMD: The Problem, Editorial. Osteo International. 18 March 2005
4. Lane, J, Russell L, Khan S. Osteoporosis. Clinical Orthopaedics and Related Research 2000;372, 139-150
5. D. B. Burr. Effects of microdamage on bone strength. Presentation at Bone Quality Meeting. Maryland, Bethesda. May 2005.
6. Mashiba T et al. Bone 2001; 28: 524-531; Day JS et al J Orthop Res 2004; 22: 465-471
7. Mori S, Burr DB. Increased intracortical remodeling following fatigue damage. Bone. 1993; 14: 103-9
8. R. Recker. Clinical relevance of microdamage accumulation and excess remodeling suppression. Presentation at Bone Quality Meeting. Maryland, Bethesda. May 2005.
9. Recker R, Lappe J, Davies KM, Heaney R. Bone remodeling increases substantially in the years after menopause and remains increased in older osteoporosis patients. J Bone Miner Res. 2004; 19:1628-33
10. Henderson J, Binette J, Li, A, Li, W, Fortin, A, Skamene, E. Comprehensive skeletal phenotyping to assess bone quality in genetically defined mice. P52 at Bone Quality Meeting. Maryland, Bethesda. May 2005
11. van Lenthe, G, Kohler, T, Voide, R, Donahue, L, Muller, R. Identifying genetic loci for bone quality parameters in murine inbred strains. P51 at Bone Quality Meeting. Maryland, Bethesda. May 2005.
12. Price, C, Jepsen KJ. Genetic variability in bone brittleness is established early in life. Young investigator award recipient, P48 at Bone Quality Meeting, Maryland, Bethesda. May 2005.
13. K.J. Jepsen. Using mice to understand structure-function relationships in the skeleton. Presentation at Bone Quality Meeting in Maryland, Bethesda. May 2005.

Last Updated ( Thursday, 03 November 2005 )