Published 7/1/2011
Adele L. Boskey, PhD

Using bone quality to assess fracture risk

Fracture risk is generally assessed by clinicians based on the amount of bone that is present (bone quantity), measured by dual energy X-ray absorptiometry (DEXA) scans, and reported as a two-dimensional measurement of bone mineral density (BMD) or as a T- or Z-score that compares that BMD to the average value for a 25-year-old white woman (T-score), or an age-, gender-, and sex-matched average (Z-score).

While BMD is a good surrogate for bone quantity, BMD accounts for less than 70 percent of the predictive fracture risk. Further, BMD changes often do not correlate with the improvement in fracture risk provided by antiresorptive or anabolic therapies. To increase predictive values and better assess the efficacy of drugs being used to treat and prevent fragility fractures, investigators also consider bone quality.

Bone quality refers to all the parameters beyond BMD that can affect fracture risk, including bone geometry and architecture, the extent of mineralization and the properties of the mineral, the presence of micro-cracks, and the amount and properties of the collagen. The techniques that can be used to assess each of these parameters were the topic of a symposium recently published in Clinical Orthopaedics and Related Research.

Introduced in the late 1980s, the techniques of infrared spectroscopic microscopy (FTIRM) and infrared spectroscopic imaging (FTIRI) enable the measurement of regional changes in bone compositional properties with less than 6 μm resolution. These properties include the relative amount of mineral present in a given area (which correlates with BMD), crystal size and perfection, carbonate substitution, and collagen maturity (cross-linking). Although these compositional data represent a number of the bone quality parameters, they do not include bone architecture, geometry, or the presence of microcracks.

To perform FTIRI or FTIRM measurements, a biopsy of a thin nondecalcified section (1–2 microns in thickness) of bone is required. Because further analysis of the biopsied sample is nondestructive, a number of other parameters (illustrated as image maps) can be determined from the same scan/biopsy. Additionally, the section can be stained or used for other bone analyses.

These techniques have been used to characterize the mineral and collagen changes in osteoporosis and to demonstrate that both crystal size and collagen maturity are predictive of fracture risk. These same parameters are altered in diseases characterized by higher than normal rates of fracture, such as osteopetrosis and osteogenesis imperfecta. Typical images of mineral content (mineral/matrix ratio), mineral crystallinity, and collagen maturity from a human osteoporotic iliac crest bone biopsy showing both cortical and cancellous bone parameters are shown in Figure 1. Figure 2 shows the calculated distributions of mineral content, crystallinity, and collagen maturity in each image. By collecting multiple images in biopsies from patients with similar diagnoses, statistical evaluation becomes possible.

Although FTIR is not designed to be used for routine diagnosis of fracture risk, other measurements, such as noninvasive nuclear magnetic resonance or Raman imaging, are being developed for this use. In the interim, working with FTIRI and FTIRM provides a way to assess the efficacy of currently accepted treatments for osteoporosis, when biopsies are available, because they offer the ability to see which bone properties, beyond BMD, have returned to normal.

Disclosure information: Dr. Boskey—Amgen Co., Bristol-Myers Squibb, DePuy, A Johnson & Johnson Company, Eli Lilly, GE Healthcare, Genzyme, GlaxoSmithKline, Johnson & Johnson, Novartis, Sanofi-Aventis, Wyeth, Zimmer; Journal of Orthopaedic Research; Calcified Tissue International; Bone; Journal of Bone & Mineral Research; Journal of Dental Research; Clinical Orthopaedics and Related Research

Adele L. Boskey, PhD, is a member of the Research Development Committee. The work described in this review was supported by National Institutes of Health (NIH) grants AR043125 and AR046121 (NIH Musculoskeletal Integrity Core Center).


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