About Osteoporosis
The world is even now dealing with an osteoporosis fracture pandemic that will likely increase in overall proportions to become economically unmanageable in the foreseeable future.
Osteoporosis Fracture
The Need for Better and Widely Available Bone Measurements
Significance of Bone Structure Measurements
Osteoporosis Fracture
The probability that a 50 year old average risk Caucasian woman will have a hip, vertebral or wrist fracture sometime during the remainder of her life is about 14% for each fracture. Impressively, about half of patients suffering a hip fracture spend some time in a nursing home. Even if patients do not enter a nursing home immediately, 14 percent find that they need to do so after having spent one year at home. The costs of these stays in the mid-1990’s were in the range of $22,000. It is reasonable to assume that that cost has increased at least 50% in the past 10 years. The Office of Technology Assessment (OTA) has estimated that only about one third of hip fracture patients regain their pre-fracture level of functioning. For example, in one study, the authors found that only 15% of hip fracture patients were able to walk without aid at 6 months post-fracture as compared with 75% before the fracture. Most distressing is the fact that death rates are particularly high among nursing home residents who suffer a hip fracture (36% versus 21% in those admitted from other settings). In fact, it is not at all uncommon to observe a slow grim inexorable sequence that appears to be triggered by a hip fracture - pain, disability, depression, isolation, and death.
While the cost in human suffering associated with the approximately 500,000 hip fractures occurring in the United States yearly (one hip fracture every minute) is almost impossible to appreciate, their monetary cost, the better part of the total $17 billion/year spent on osteoporosis, is stunning. This is all the more alarming considering the fact that it has been difficult to see a great deal of progress in the prevention of hip fractures.
The Need for Better and Widely Available Bone Measurements
The systems that are currently available on the market for the diagnosis of osteoporosis are limited to measuring bone mineral density (BMD). BMD of patients with osteoporotic fractures is generally found to be lower than that of age-matched non-fractured controls. However, substantial overlap exists in the distribution of BMD of patients with and without osteoporotic fracture. Furthermore, BMD does not accurately predict the presence of osteoporotic fractures. Thus, although a relationship between BMD and fracture risk has been shown, other factors not accounted for in the BMD measurement are understood to influence fracture risk. Key factors among these are alterations and disruption of trabecular structure and architecture. The progressive increase in alterations and disruption of trabecular structure and architecture is a primary reason that bone from older individuals fractures at a much lower threshold than bone from young people, even at the same value for BMD.The vast majority of patients with OP are undiagnosed despite the fact that early detection and treatment can reduce the risk of fracture. This is because there are major drawbacks and bottlenecks in diagnosing OP using dual x-ray absorptiometry (DXA). DXA has limited presence in acute medical care centers because equipment is expensive ($50k-$95k per machine) and requires a lot of space. Even more importantly, DXA cannot measure bone structure/quality, parameters that are rapidly gaining importance in determination of risk for osteoporotic fractures.
Patients receiving osteoclast inhibiting, anti-resorptive drugs show remarkable reductions in incident osteoporotic fractures by 60-65% but only small changes in BMD on the order of 4.0-4.5%, strongly indicating a significant discrepancy between clinical outcomes and traditional non-invasive measurements of bone health. This means that it is neither possible to identify specific individuals who need treatment to prevent impending fracture or to monitor their response to treatment to determine if their fracture risk has been reduced. It also adds to the already high cost of developing new osteoporosis drugs. This is because those clinical trials must rely on large patient cohorts entailing several thousand patients followed over several years in order to detect statistically significant differences in the incidence of new osteoporotic vertebral fractures between treatment and placebo groups.
Significance of Bone Structure Measurements
There is a significant need for non-invasive measurements of bone structure and architecture in addition to assessment of BMD. The structural characteristics of trabecular bone are an important consideration for fracture risk. Recent micro-CT data in bone biopsy specimen obtained in normal premenopausal women and then in the same group of women sampled 12 months after menopause show that there are dramatic changes in bone structure, specifically in 3D trabecular bone volume fraction (-5.4%/yr), trabecular thickness (-3.3%/yr), trabecular separation (+2.0%/yr), and structure model index (+11.3%/yr) after menopause [9]. Unfortunately, CT is limited to in vitro studies of bone specimens. Nonetheless, these data show how powerful a non-invasive test for in vivo assessment of bone structure could be.
The Singh index provided a first indication that changes in the trabecular pattern of the upper end of the femur can be used for the diagnosis and staging of osteoporosis. However, several groups reported only a limited correlation between the Singh index and bone mineral density measured by DXA. This is not surprising since both measure different properties of bone. Several investigators have reported a good correlation between the Singh index and osteoporotic fractures, the primary outcome variable in osteoporosis. The Singh index, being a subjective evaluation, is highly dependent on the experience and knowledge of the observer.
Simple geometric measurements and subjective evaluation of trabecular structure made on conventional radiographs of the hip have been reported as useful for differentiating normal subjects and women with osteoporotic hip fracture. In the study by Gluer et al., these measurements included thickness of the femoral shaft cortex and of the femoral neck cortex, an index of tensile trabeculae, and a wider trochanteric region. The combination of these four measurements predicted hip fracture at least as strongly as did measurement of bone density of the femoral neck (areas of the receiver-operating characteristic curve = 0.81 and 0.80, respectively).
