Consensus Summary on the Diagnosis and Treatment of Osteoporosis

A consensus conference was constituted under the auspices of the journal Spine to address the diagnosis, treatment, and prevention of osteoporosis. Osteoporosis is characterized by decreased bone mass and an increased susceptibility to fracture. The current issue of Spine contains a series of articles that relate our current understanding of the pathophysiology of osteoporosis and provide therapeutic strategy to control and rectify the skeletal fragility of this disorder. Highlights of that meeting follow: (participants: Melton, Myers, Seeger, Eyre, Glazer, Bostrom, Hu, Weinstein, Anderson, and Lane). Epidemiology Osteoporosis is one of the most common chronic diseases, along with hypertension and diabetes mellitus. Based on the World Health Organization criteria, about a third of postmenopausal white women have osteoporosis. The prevalence of osteoporosis is less at specific skeletal sites. A little more than 20% of white women older than age 50 have osteoporosis of the hip, but the rates are lower for Hispanic and African-American women (16% and 10%, respectively). The prevalence of osteoporosis of the lumbar spine in women older than age 50 is approximately 16% and, after correction for skeletal size, is similar among women of other ethnic groups. Most types of fractures in older individuals are due, in part, to reduced bone strengths associated with osteoporosis. The lifetime risk of any fracture among white women from age 50 onward approaches 75%. The lifetime risk of a hip fracture is 17% in white women and approximately 6% in white men. The risk is lower among nonwhites. The lifetime risk of a clinically evident vertebrae fracture is approximately 16% among white women, with comparable risk among Asian women. The risk of osteoporotic fractures increases dramatically with aging. The incidence of hip fractures increases exponentially with aging in men and women of all races, and the incidence of clinically detected vertebral fractures increases approximately sixfold between the ages of 45 and 85. Vertebral fractures are as frequent in men as in women. Despite the widespread belief that osteoporosis is a disorder of women, recent studies from around the world indicate that the prevalence of vertebral fractures is as great in men as in women, affecting approximately one fourth of each group, depending on the definition of vertebral fracture used. It is not possible to predict in whom osteoporosis will develop. Osteoporosis may result either from inadequate skeletal development (small peak bone mass) or from excessive bone loss, each the result of complex genetic and environmental influences. A number of risk factors have been identified that are sufficiently widespread to provide an index of suspicion for that condition. However, these risk factors, alone or in combination, are not sufficient to reliably predict bone density in an individual patient. Several large, population-based studies are producing a wealth of new data that should provide new insights about the etiology of osteoporosis and fractures. Biomechanics of Osteoporosis and Vertebral Fracture Vertebral bone in the aging spine fails because it cannot support the internal stresses that result from loads applied to the spine. The strength of the trabecular bone in the vertebral centrum is determined by apparent density and by trabecular architecture. Reductions in density and thinning and loss of trabeculae result in corresponding reductions in strength. The failure load of a vertebral body is determined by the strength of the trabecular bone in the centrum and by the geometry and structural organization of the vertebral body. Bone mineral density values from noninvasive techniques such as dual-energy x-ray absorptiometry capture aspects of bone density and geometry and have a direct, positive relation with the compressive failure load of the vertebral body for white women and men. This relation needs to be defined for other races. Based on biomechanical studies, assessment of bone mineral density in vivo should indicate the peak compressive load that can be carried by the vertebral body. Bone strength and load-bearing should be considered in relation to the forces applied to the spine during normal activities or trauma. The ratio of loads applied to the spine during specified activities divided by the failure load of the vertebral body is called the factor of risk. Factors of risk greater than one mean that the load on the vertebra exceeds the structural capacity and suggests that fracture is likely to occur. Vertebral fractures occur under a heterogeneous set of circumstances. Activities associated with fractures include falls and controlled activities such as lifting, but approximately half of vertebral fractures are not attributed to a known loading activity. Such spontaneous fractures may be the result of fatigue damage from loading during normal activities. Everyday activities such as lifting a moderate weight can result in factors of risk greater than one for subjects with low vertebral bone mineral density. Future directions in biomechanics research include investigating the effects of turnover state on bone strength and fracture risk. Diagnosis-Bone Density and Biochemical Markers Bone density determination is indicated for perimenopausal women determining their need for hormonal replacement therapy, to evaluate patients with metabolic bone disease that affects the skeleton, to evaluate patients on medicines that affect the skeleton, to evaluate patients with a high number of osteoporotic risk factors, to monitor the efficacy of treatment, and to evaluate premenopausal women with prolonged amenorrhea. The test to perform depends on the availability of the equipment, with most therapeutic guidelines based on dual-energy x-ray absorptiometry measurement. The densitometry results need clinical correlation with all risk factors, exclusion of other lesions, and biochemical markers of bone turnover. The bone mineral density of one site predicts the fracture risk at that site and at other sites in the population but not for that individual patient. The proximal femur is the best site for determination for hip fracture risk. There is a continuum between decreasing bone mineral density and fracture risk. Density determination is supported for both the spine and hip at the initial encounter. There is variability between equipment, and results are subject to the artifacts of vascular calcification, degenerative disc disease, osteoarthritis of the posterior elements, and obesity. Standardization of bone density equipment and normative standards are required. Bone formation markers are bone-specific alkaline phosphatase and osteocalcin in the serum. In general, they reflect collective osteoblast activity in the skeleton. Currently, the most specific bone resorption markers are degradation products of collagen in urine, in particular the pyridinoline cross-links (pyridinoline and deoxypyridinoline) and cross-linked telopeptides of type 1 bone collagen (NTX and CTX). The individual markers may reflect different tissue origins and metabolic pathways, however. Both resorption and formation markers can provide an index of total bone turnover. They normally change in unison through the coupling phenomenon, with formation lagging behind resorption by several months, as occurs with the early postmenopausal increase in turnover or in the short-term response to antiresorptive therapy (estrogen, hormone replacement, bisphosphonates, Vitamin D, and calcium). Bone markers are not equivalent to bone density. The latter establishes where the patient is in terms of skeletal bone mass, and the markers indicate where she is going. High turnover, as indicated by biochemical markers, is a predictor of future fracture independent of bone mineral density. High turnover is a predictor of accelerated bone loss (assessed by bone density) in early postmenopause. Future need for a better understanding of individual marker biology, tissue origins, metabolism, and resultant specificity. The issue of variability needs to be addressed. Medical Management of Osteoporosis The medical treatment of osteoporosis starts with prevention. The therapeutic thresholds are drug specific. All individuals require age-corrected physiologic doses of calcium and Vitamin D. These nutrients are critical for achieving peak bone mass in the adolescent and young adult, for maintaining bone mass during premenopause, and for limiting secondary hyperparathyroidism during postmenopause. In the elderly, calcium and Vitamin D can decrease hip fracture. Estrogen is a cost-effective and resorptive agent for the treatment of postmenopausal osteoporosis. Not only does it prevent bone loss and fragility fractures (50%), but it is a potent inhibitor of cardiovascular disease. Additional benefits include prevention of postmenopausal symptoms, improved genito-urinary physiology, limitation of Alzheimer's disease, improved cognition, and limitation of tooth loss. It is associated with increased risk of uterine cancer (preventative with co-use of progestins) and an increased risk for breast cancer during the early postmenopausal years (50-65) after 5 years of therapy, and in older patients after 10 years. Nevertheless, estrogen therapy leads to longer survival based largely on its cardiac benefit. Calcitonin as a nasal preparation is effective in high turnover spinal osteoporosis. In cohort studies, it appears to limit the risk of vertebral fracture. It also provides analgesia, possibly by way of elevated endorphins. Bisphosphonates (alendronate) inhibit osteoclastic bone resorption. They lead to increased bone mass in both the spine and hip as well as decrease fracture by 50% at these sites. The therapeutic threshold for the initiation of this class of agents is not only related to bone mass but also to the number of risk factors and level of bone turnover, both of which suggest earlier initiation. Lower formulations are now available for prevention. New classes of bisphosphonates, slow release fluoride, PTH-P analgesics, and SERMs (selective estrogen response modifiers) are undergoing clinical trials. The SERMs specifically prevent breast cancer yet protect in the skeleton. Several of the agents hold a potential to treat low-turnover osteoporosis. Exercise is beneficial for the skeleton. Impact exercises, strengthening, and balance programs (Tai Chi) can result in a lower fracture rate. Specifically, Tai Chi can lower falls by 47%. Future directives are aimed at creating therapeutic thresholds for the emerging therapies. Spinal Instrumentation in Patients With Osteoporosis Most osteoporotic compression fractures are asymptomatic. Surgical intervention is rarely indicated for osteoporotic compression fractures. If patients with osteoporosis are in need of spinal surgery, they should be evaluated for potential malnutrition, as well as insuring that patients have adequate calcium and Vitamin D intake. Additional medical pretreatment may be appropriate for selected patients. When surgery is indicated for patients with osteoporosis, instrumentation may not be advisable, except in cases of deformity or gross instability. Surgical principles, which should be applied when instrumenting patients with osteoporosis, include: use of segmental fixation, avoidance of ending the fusion at a kyphotic segment, and avoidance of use of sublaminar wires at the ends of constructs. There may be use in the future of new biomaterials to improve fixation in these patients' augmentation, or use of growth factors to speed fusion. There is a need for development of instrumentation whose material properties would allow for rigid fixation and bone healing, without affecting adjacent levels.