Efficacy of teriparatide and alendronate on nonvertebral fractures.
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Biomedical subjects
Publications and source records attributed to Nelson B Watts.
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We reviewed the epidemiology, diagnosis, and treatment of vertebral fractures due to osteoporosis in the elderly. Vertebral fractures are underdiagnosed despite their high prevalence in both men and women. Clinical consequences of vertebral fractures include increased risk of future vertebral and hip fracture, acute and chronic back pain, decreased quality of life, and increased mortality. Patients with vertebral fractures have functional impairment and increased mortality similar to those with hip fractures. Asymptomatic fractures identified on radiograph also affect quality of life and mortality. A vertebral fracture is a clinical marker for a subsequent fracture and should trigger assessment and diagnosis of osteoporosis. The care of patients with vertebral fractures includes pain management, rehabilitation, and prevention of further fractures. There is evidence from randomized controlled trials that pharmacologic therapy can reduce the risk of future fractures by 40% to 50%. Vertebroplasty may be effective in the control of pain and in obtaining stability of the spine.
Oncogenic osteomalacia, an acquired hypophosphataemic syndrome associated with mesenchymal tumours, is characterised by hypophosphataemia secondary to inappropriate phosphaturia, reduced concentrations of serum calcitriol, and defective bone mineralisation. Removal of these tumours results in complete reversal of these biochemical defects. However, because these tumours are small, slow-growing, and frequently situated in unusual anatomical sites, conventional imaging techniques often fail to detect them. Since mesenchymal tumours express somatostatin receptors, we postulated that somatostatin analogues would be able to detect these tumours. We did Indium-111 labeled pentetreotide imaging in seven patients with oncogenic osteomalacia. In five patients, we identified a mesenchymal tumour, and clinical improvement occurred after tumour resection. Our findings suggest that 111In-pentetreotide imaging effectively detects occult mesenchymal tumours and facilitates surgical treatment of oncogenic osteomalacia.
A number of agents have been shown to reduce the risk of fractures in patients with postmenopausal osteoporosis. However, the additional benefits of combination therapy as opposed to monotherapy are uncertain. We performed a MEDLINE search and reviewed the published randomized trials of agents used in combination. Combination therapy results in greater gains in bone mineral density than monotherapy and possibly greater effects on bone turnover. However, none of these studies are large enough or of sufficient duration to determine whether a greater reduction in fracture is achieved. Combination therapy has important cost implications and is likely to be associated with an increased prevalence of adverse events, reduced tolerability and a reduction in adherence. Furthermore, over-suppression of bone turnover as a result of combination antiresorptive therapy might have adverse effects on bone strength, particularly with long-term treatment. Thus, the use of combination therapy for treatment of osteoporosis cannot be recommended on the basis of currently available evidence.
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Bone densitometry is routinely used to assess the skeleton in patients who have diseases or conditions that can cause low bone mass. However, there are some areas of controversy related to the interpretation of bone densitometry results. To address these issues, the International Society for Clinical Densitometry (ISCD) convened a Position Development Conference in Denver, Colorado, July 20-22, 2001. The ISCD is a not-for-profit multidisciplinary society whose main mission is to promote quality in the performance and interpretation of bone densitometry examinations.
Given the need for authoritative positions in areas of controversy in the field of bone densitometry, the International Society for Clinical Densitometry (ISCD) convened a Position Development Conference in Denver, CO, USA, in July 2001. Four general areas were selected on the basis of clinical importance and likelihood of reaching agreement. These areas were discussed at length prior to the conference by the Scientific Advisory Committee of the ISCD and presented to a panel of experts at the conference. The four areas included discussions of (1). the regions of interest of central dual X-ray densitometry (DXA), (2). the criteria by which a densitometric diagnosis of osteoporosis can be made in men and non-Caucasian women, (3). the role of serial BMD measurements in patient management, and (4). the standards by which bone mass measurements at peripheral sites should be used in the diagnosis of osteoporosis. Details of the methodology used at the conference are discussed. The following papers explain the results of the discussions and describe the official ISCD positions.
BACKGROUND: Pyridinoline (PYD) and deoxypyridinoline (DPD) are two of the most extensively characterized biochemical bone markers, but the interpretation of results is hampered by biologic and other preanalytical variability. We reviewed factors contributing to preanalytical variation of pyridinium cross-links in urine. METHODS: We searched four databases for English-language reports on PYD and/or DPD in urine. Searches were restricted to humans, except for studies of stability, when the search was expanded to other species. The 599 identified articles were supplemented with references from those articles and with articles known to the authors. RESULTS: The mean reported within-day variability was 71% for PYD (range, 57-78%) and 67% for DPD (range, 53-75%). The mean interday variability was 16% for both DPD and PYD (range for PYD, 12-21%; range for DPD, 5-24%). The mean intersubject variabilities across studies were 26% for PYD (range, 12-63%) and 34% for DPD (range, 8-98%) for healthy premenopausal women and 36% (range, 22-61%) and 40%, (range, 27-54%) for postmenopausal women, respectively. Specimen instability and errors in creatinine measurements were additional sources of variability. CONCLUSIONS: Intra- and intersubject variability can be reduced by collecting specimens at a specific time of the day and by maintaining similar patient status at each specimen collection regarding factors such as medications and dietary supplements.
Osteoporosis is a skeletal disorder that is associated with lowered bone mineral density and increased risk of fracture. Numerous clinical trials have been conducted to study drugs and lifestyle changes that can either prevent bone loss in perimenopausal women or prevent fractures in women with established osteoporosis. The role of estrogen alone or in combination with androgen as hormone replacement therapy is discussed for its potential value in osteoporosis prevention and treatment. Additional therapies that are examined for prevention and treatment of osteoporosis include tibolone, bisphosphonates (alendronate and risedronate), selective estrogen-receptor modulators, calcitonin and parathyroid hormone. Experimental therapies that are in different phases of evaluation in osteoporosis management include statins as well as tumor necrosis factor-receptor antagonists. Other strategies include nonpharmacologic interventions, such as calcium supplements, vitamin D and exercise.
OBJECTIVE: Recent randomized clinical trials have shown that risedronate reduces the risk of nonvertebral fractures and clinical vertebral fractures within 6 months of initiating treatment. The objective of the current study was to determine whether this early antifracture effect could be demonstrated in nonvertebral fractures for risedronate and other osteoporosis therapies in an observational administrative claims database. METHODS: A proprietary administrative claims database was used to identify managed care members who received a new prescription for risedronate, alendronate, or nasal calcitonin from July 1, 2000, to December 31, 2001. Patient records were analyzed for the incidence of nonvertebral fractures (clavicle, humerus, wrist, pelvis, hip, and leg) in the first 6 and 12 months following initiation of treatment. A Cox proportional hazards regression model was used to estimate relative risk (RR) of fracture at 6 and 12 months. RESULTS: In the 6-month analysis, 774 patients (11%) received calcitonin, 5,307 (75%) received alendronate, and 1,000 (14%) received risedronate. Twelve-month data were available for a subset (71%) of patients (656 calcitonin [13%], 3,716 alendronate [74%], and 652 risedronate [13%]). Most were women (93%); mean age was similar for alendronate and risedronate, and nasal calcitonin patients were about 3 years older, on average. Risedronate and alendronate patients were more likely to have used estrogen, while nasal calcitonin patients were more likely to have been hospitalized and had higher use of concomitant medications and more physician visits. Relative risks were adjusted for these differences. Risedronate and alendronate patients were similar with respect to these indicators of general health status. In the 6-month analysis, nonvertebral fractures were observed in 2.2% of patients receiving nasal calcitonin, 1.4% of patients receiving alendronate, and 0.6% of patients receiving risedronate. The adjusted RR reduction was 69% for risedronate versus calcitonin (RR = 0.31; 95% CI, 0.12 to 0.81; P = 0.02), 54% for risedronate versus alendronate (RR = 0.46; 95% CI, 0.20 to 1.06; P = 0.07), and 26% for alendronate versus calcitonin (RR = 0.74; 95% CI, 0.43 to 1.27; P = 0.28). In the 12-month analysis, nonvertebral fracture rates were 2.9% for nasal calcitonin, 2.4% for alendronate, and 0.9% for risedronate patients. The adjusted RR reduction was 75% for risedronate versus calcitonin (RR = 0.25; 95% CI, 0.10 to 0.64; P<0.01), 59% for risedronate versus alendronate (RR = 0.41; 95% CI, 0.18 to 0.94; P = 0.04), and 25% for alendronate versus calcitonin (RR = 0.75; 95% CI, 0.45 to 1.25; P = 0.27). CONCLUSIONS: This analysis of medical and pharmacy claims contained in an administrative database confirms the early fracture reduction with risedronate that was shown in randomized clinical trials. Risedronate was more effective than calcitonin in reducing the risk of nonvertebral fractures within the first 6 months of treatment. Risedronate was more effective than either calcitonin or alendronate in reducing the risk of nonvertebral fractures within 12 months of treatment.
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