Foundation Bone density vs bone quality: What’s a ...

1 REVIEW. Angelo Licata, MD, PhD*. Director, Center for Space Medicine; Consultant, Depart- ments of Biomedical Engineering and Endocrinology, Diabetes, and Metabolism, Metabolic bone Center, cleveland clinic ; Editor-in-Chief, Clinical Reviews in bone and Mineral Metabolism; Editor-In-Chief, National Osteoporosis Foundation Osteoporosis Clinical Updates bone density vs bone quality : What's a clinician to do? Abstract M ost clinicians were taught directly or indirectly that bone density is the gauge for assessing bone strength and the response Studies of the epidemiology of osteoporosis and of drug treatments for it have challenged the concept that denser to antiosteoporotic treatment. In recent years, bone means stronger bone . bone strength or resistance to however, the concept of bone strength has fracture is not easily measured by routine densitometry, moved beyond density alone and has expanded to include a number of characteristics of bone being a function of both density and quality .

2 That collectively are called quality . Key Points This paper describes how the notion of quality has emerged and some of the clinical bone quality is a composite of properties that make bone scenarios in which quality applies. It discusses resist fracture, such as its microarchitecture, accumulated several observations in the clinical literature microscopic damage, the quality of collagen, mineral that challenge our understanding of bone den- crystal size, and bone turnover. sity and strength and provides the practitioner a better understanding of densitometry in clin- ical practice. The T score was derived from a population of white women in their mid to late 60s and older; in other popu- WHAT IS bone quality ? lations, low T scores do not necessarily reflect the dis- ease state osteoporosis with its inherent decreased bone quality is not precisely defined.

3 It is de- strength and propensity to fracture. scribed operationally as an amalgamation of all the factors that determine how well the In assessing the risk of fractures, clinicians should con- skeleton can resist fracturing, such as micro- sider not only the bone mineral density but also clinical architecture, accumulated microscopic dam- risk factors. age, the quality of collagen, the size of mineral crystals, and the rate of bone turnover. The term became popular in the early 1990s, when Markers of bone turnover are elevated in some cases of paradoxes in the treatment of osteoporosis primary osteoporosis and return to normal levels with challenged the generally accepted orthodoxy antiresorptive therapy but not with anabolic therapy. that bone density itself was the best way to as- sess strength of bone .

4 FROM bone MASS TO T SCORES. TO bone quality . Today's practitioners appreciate the impor- *. The author has disclosed that he has received honoraria from the Eli Lilly, Merck, and Novartis tance of the T score in diagnosing osteoporo- companies for teaching and speaking. sis. It was not always this way, since the early attempts to use bone densitometry focused on CL EV E L AND CL I NI C J O URNAL O F M E DI CI NE V O L UM E 76 NUM BE R 6 J UNE 2009 331. bone quality ficient to accurately make such a diagnosis Fluoride looks good as a treatment in patients outside the demographic group if we look only at density in which it was developed, because the low 12 disease prevalence in younger groups makes the score less accurate as a predictive tool. Moreover, reevaluation of data from pivotal 10 clinical trials has brought into question our Change in bone mass (% year).

5 Long-held idea that increases in bone den- 8 sity parallel increases in bone strength and reduction in fractures, and that therapeutic improvement in bone density is the mark of 6 success. bone strength or resistance to frac- ture is more complex than density alone. Into 4 this arena enters the concept of bone quality , r = which attempts to explain the following ob- P < .0011 servations. 2. DENSER bone . 0 IS NOT ALWAYS STRONGER. 0 20 40 60 80 The first inkling of the discrepancy between Sodium fluoride dose (mg/day) density and strength arose with the use of so- dium fluoride to treat osteoporosis. Although FIGURE 1. Although the dose-response curve indicates sodium fluoride produced large increases in that sodium fluoride increases bone mass, this drug bone mass (and therefore in density ) (Figure actually increases the fracture rate because it makes 1), the strength of the bone did not parallel bone more brittle.

6 This ,6 In fact, fluoride made bone Kleerekoper M, Balena R. Fluorides and osteoporosis. AnnU Rev Nutr 1991; 11:309-324. reprinted with permission 1991 from annual reviews, more brittle, because it changed the quality of the mineral and rendered it more suscep- tible to fracturing. High serum fluoride levels increased the vertebral fracture rate despite a specific cutoff of bone mass as a risk for frac- higher bone ture and not the statistical T scores or Z scores that we 3 Not all low bone MINERAL density . The T score concept was originally de- is osteoporosis veloped to assess the probability of fragility fractures in postmenopausal white women in The following case describes a clinical scenar- their mid to late 60s and It has been io in which a patient has low bone density but useful because the disease prevalence is high does not have osteoporosis.

7 In this age group. The T score as originally used was a surrogate marker for the histolog- A young healthy woman ic changes in aged bone that render it weak with low bone density and susceptible to fractures from low load- A 35-year-old healthy woman who has jogged ing forces: the lower the score, the worse recreationally for decades is evaluated for pos- the fracture risk. It followed intuitively that sible treatment of osteoporosis. She started to a low T score clinched the diagnosis of pri- feel back pain after doing heavy work in her mary osteoporosis. garden. Spinal radiographs did not show a rea- But the T score has its problems when son for her pain, but her physician, concerned used outside this intended population. Prac- about osteopenia, sent her for dual-energy x-ray titioners have assumed that all patients with absorptiometry.

8 Her spinal T scores and Z scores abnormally low scores have primary osteopo- were standard deviations below the mean. rosis. However, this number alone is insuf- Should she start pharmacologic therapy? 332 CLEV ELA N D C LI N I C JOURNAL OF MEDICINE VOL UME 76 N UM BE R 6 J UNE 2009. LICATA. Young bone is stronger than older bone At any T score, young bone This case shows the other end of the spectrum from the fluoride story. Here, a young healthy is stronger than older bone person inappropriately underwent a density 160 Age (years). scan, which led to confusion about how to in- terpret the results. As stated above, T scores are not appropriate 140 80+. for young patients the Z score is used instead. In this case, the low value implied deficiency of Fracture risk per 1,000 person-years bone mass compared with age-matched norms.

9 120. However, in this patient with no clinical risk factors for fracture, a low T score meant that 75-79. her bone density was low, but not that she had 100. osteoporosis. Several factors could account for her low bone density . It could be genetic, if her family 80 70-74. is small in stature, or she could be at the ex- treme end of the distribution curve for normal 60. individuals. Runners tend to be slight in build, 65-69. and so may have lighter bones. Furthermore, for women, excessive running could lead to 40 60-64. lower estrogen activity and therefore lower bone mineral density . 55-59. Drug treatment is not warranted for this 20 50-54. patient, but standard therapy with exercise, 45-49. vitamin D, and adequate elemental calcium < 45. from the diet or supplements is reasonable. 0. Two decades ago, in one of the first indica- > < tions that something besides bone density was critical to strength, a hallmark study showed bone mass (g/cm).

10 That fracture rates are dramatically different FIGURE 2. Estimated incidence of fracture as a function across similar levels of bone mass or T scores of age and bone mass in 521 white women followed for depending on a person's age (figure 2).7 Many an average of years. subsequent observations also brought into Hui SL, Slemenda CW, Johnston CC Jr. Age and bone mass as predictors of fracture in question how important density ,9 a prospective study. J Clin Invest 1988; 81:1804 1809. Thus, the notion of quality entered the clinical arena. Young bone and older bone are qualitatively different in strength, even with for treating osteoporosis prevented fractures bet- similar bone density . This difference was later ter than we would expect from their effects on found to be related to significant qualitative bone density .