Changing perceptions in osteoporosis. Markers should be used as adjunct to bone densitometry.
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Biomarkers↗
Biomedical subjects
N B Watts
Publications and source records attributed to N B Watts.
Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial. Vertebral Efficacy With Risedronate Therapy (VERT) Study Group.
CONTEXT: Risedronate, a potent bisphosphonate, has been shown to be effective in the treatment of Paget disease of bone and other metabolic bone diseases but, to our knowledge, it has not been evaluated in the treatment of established postmenopausal osteoporosis. OBJECTIVE: To test the efficacy and safety of daily treatment with risedronate to reduce the risk of vertebral and other fractures in postmenopausal women with established osteoporosis. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, placebo-controlled trial of 2458 ambulatory postmenopausal women younger than 85 years with at least 1 vertebral fracture at baseline who were enrolled at 1 of 110 centers in North America conducted between December 1993 and January 1998. INTERVENTIONS: Subjects were randomly assigned to receive oral treatment for 3 years with risedronate (2.5 or 5 mg/d) or placebo. All subjects received calcium, 1000 mg/d. Vitamin D (cholecalciferol, up to 500 IU/d) was provided if baseline levels of 25-hydroxyvitamin D were low. MAIN OUTCOME MEASURES: Incidence of new vertebral fractures as detected by quantitative and semiquantitative assessments of radiographs; incidence of radiographically confirmed nonvertebral fractures and change from baseline in bone mineral density as determined by dual x-ray absorptiometry. RESULTS: The 2.5 mg/d of risedronate arm was discontinued after 1 year; in the placebo and 5 mg/d of risedronate arms, 450 and 489 subjects, respectively, completed all 3 years of the trial. Treatment with 5 mg/d of risedronate, compared with placebo, decreased the cumulative incidence of new vertebral fractures by 41 % (95% confidence interval [CI], 18%-58%) over 3 years (11.3 % vs 16.3%; P= .003). A fracture reduction of 65% (95% CI, 38%-81 %) was observed after the first year (2.4% vs 6.4%; P<.001). The cumulative incidence of nonvertebral fractures over 3 years was reduced by 39% (95% CI, 6%-61 %) (5.2 % vs 8.4%; P = .02). Bone mineral density increased significantly compared with placebo at the lumbar spine (5.4% vs 1.1 %), femoral neck (1.6% vs -1.2%), femoral trochanter (3.3% vs -0.7%), and midshaft of the radius (0.2% vs -1.4%). Bone formed during risedronate treatment was histologically normal. The overall safety profile of risedronate, including gastrointestinal safety, was similar to that of placebo. CONCLUSIONS: These data suggest that risedronate therapy is effective and well tolerated in the treatment of women with established postmenopausal osteoporosis.
Aged↗
Alendronate increases spine and hip bone mineral density in women with postmenopausal osteoporosis who failed to respond to intermittent cyclical etidronate.
In a U.S. multicenter study of intermittent cyclical etidronate treatment for postmenopausal osteoporosis, approximately 20% of patients were nonresponders, defined as failure to increase spine bone mineral density. In contrast, essentially all patients who received 10 mg of alendronate daily in U.S. phase III trials showed some increase in spine bone mineral density. The current study was undertaken to determine the response to alendronate therapy in women with postmenopausal osteoporosis who were nonresponders to intermittent cyclical etidronate therapy. Twenty-five women with postmenopausal osteoporosis (mean +/- SD: 65.1+/-1.9 years of age), previously treated with intermittent cyclical etidronate with no increase of spine bone mineral density, and who agreed to be changed to alendronate, were recruited from a university out-patient clinic specializing in the treatment of osteoporosis for a prospective observational study. Measurements included bone mineral density of the lumbar spine and proximal femur (by dual-energy X-ray absorptiometry) and biochemical markers of bone remodeling (serum bone-specific alkaline phosphatase by immunoassay and urine deoxypyridinoline by high-pressure liquid chromatography). Patients had received intermittent cyclical etidronate for 3.3+/-0.4 years, during which time their bone density declined at spine and hip sites. They were then changed to alendronate 10 mg/day, which they received for 1.3+/-0.1 years; after treatment with alendronate, bone mineral density increased significantly at the lumbar spine (4.4+/-0.7% annualized,p < 0.0001) and at all hip sites. Bone markers also changed significantly after alendronate treatment: urine deoxypyridinoline fell from 6.8+/-0.8 to 5.5+/-0.6 micromol/mol creatinine (p < 0.0001) and serum bone-specific alkaline phosphatase rose from 4.6+/-0.5 to 11.9+/-1.0 ng/mL (p < 0.0001). Upper gastrointestinal side effects forced 4 of 25 patients (16%) to discontinue alendronate. Alendronate increases bone density at the spine and hip in patients who have not responded to intermittent cyclical etidronate therapy. Changes in bone markers suggest that alendronate causes more complete suppression of bone resorption and less inhibition (or stimulation) of bone formation.
Absorptiometry, Photon↗
Postmenopausal osteoporosis.
UNLABELLED: Osteoporosis affects approximately 28 million Americans and costs about $14 billion a year. Low bone density is the most important risk factor for osteoporosis. The National Osteoporosis Foundation recommends bone density testing for all women over 65 and earlier (around the time of menopause) for women who have risk factors or who are considering therapy. Biochemical markers of bone remodeling, such as urine collagen cross links, may be useful to decide if treatment is needed and to determine the effectiveness of treatment. Once the diagnosis of osteoporosis is made, it is time to consider management options. A healthy life style is important for everyone: an adequate intake of calcium and vitamin D and regular weight-bearing exercise. Pharmacologic agents are indicated for all patients with fragility fractures and for many patients with low bone density. Estrogen is the agent of choice for both prevention and treatment of postmenopausal osteoporosis; however, once estrogen is stopped, bone mass levels drop fairly quickly. Long-term adherence to hormone replacement therapy is not good. Effective alternatives for prevention of bone loss in recently menopausal women include alendronate (a bisphosphonate) and raloxifene (a selective estrogen-receptor modulator). Effective alternatives for treatment of established osteoporosis include alendronate and nasal calcitonin. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians LEARNING OBJECTIVES: After completion of this article, the reader will be able to understand the clinical impact and sequlae of osteoporosis in women, how to identify the high risk patient and those patient that should be screened, the various tests that are available for screening and monitoring, and the various pharmacologic therapies for osteoporosis.
Biomarkers↗
Understanding the Bone Mass Measurement Act.
The Bone Mass Measurement Act (BMMA) set forth regulations to provide for uniform coverage under Medicare Part B for bone mass measurements for services provided on or after July 1, 1998. The BMMA authorizes Medicare coverage of "medically necessary approved measurements" performed for a "qualified individual" who falls into at least one of five diagnostic categories: an estrogen-deficient woman at clinical risk for osteoporosis; an individual with vertebral abnormalities; an individual receiving long-term glucocorticoid (steroid) therapy; an individual with primary hyperparathyroidism; and an individual being monitored to assess the response to, or efficacy of, an approved osteoporosis drug therapy. Proper communication is essential for reimbursement. The tools for communication include Physician's Current Procedural Terminology (CPT), HCFA (Health Care Financing Administration) Common Procedure Coding System (HCPCS), the Medicare carrier's local Medical Review Policy (LMRP), and the International Classification of Diseases, ninth revision (ICD-9). This article reviews the new regulations and the tools for communication.
Absorptiometry, Photon↗
Practical clinical application of biochemical markers of bone turnover: Consensus of an expert panel.
Biochemical markers of bone turnover have emerged as powerful tools to aid in managing osteoporosis. The newer bone markers have been intensively studied for more than a decade. As a result, we can now confidently report their clinical utility in assessing risk of rapid bone loss and fracture, and monitoring therapy in postmenopausal women with or at risk of osteoporosis. In this review, we will provide a comprehensive foundation for this utility. While there are still questions remaining to be answered, bone marker technology has matured to play an essential role in patient management. We will describe, in practical terms, how bone markers can be appropriately incorporated into clinical practice today.
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Clinical utility of biochemical markers of bone remodeling.
Remodeling is essential for bone health. It begins with resorption of old bone by osteoclasts, followed by the formation of new bone by osteoblasts. Remodeling is coupled (formation is linked to resorption). After middle age or perhaps beginning earlier, bone loss occurs because resorption exceeds formation. This imbalance is accentuated by estrogen deficiency as well as by many diseases and conditions. Biochemical markers that reflect remodeling and can be measured in blood or urine include resorption markers (e.g., collagen cross-links) and formation markers (e.g., alkaline phosphatase). Bone markers exhibit substantial short-term and long-term fluctuations related to time of day, phase of the menstrual cycle, and season of the year, as well as diet, exercise, and anything else that alters bone remodeling. These biological factors, in addition to assay imprecision, produce significant intra- and interindividual variability in markers. Bone marker measurements are noninvasive, inexpensive, and can be repeated often. Unfortunately, most of the studies that provided insight on clinical situations did not focus on markers as a primary endpoint. Bone markers have been useful in clinical practice and have been helpful in understanding the pathogenesis of osteoporosis and the mechanism of action of therapies. In clinical trials, markers aid in selecting optimal dose and in understanding the time course of onset and resolution of treatment effect. Clinical questions that might be answered by bone markers include diagnosing osteoporosis, identifying "fast bone losers" and patients at high risk of fracture, selecting the best treatment for osteoporosis, and providing an early indication of the response to treatment. Additional information is needed to define specific situations and cut points to allow marker results to be used with confidence in making decisions about individual patients.
Biomarkers↗
Treatment of osteoporosis with bisphosphonates.
Several bisphosphonates are effective for preventing bone loss associated with estrogen deficiency, glucocorticoid treatment, and immobilization, and for at least partially reversing bone loss in patients with postmenopausal osteoporosis and steroid-induced osteoporosis. The most promising of these agents are etidronate, alendronate, risedronate, and ibandronate. These drugs should have an important role in the prevention and treatment of osteoporosis; however, more research is needed regarding optimal doses and regimens (continuous versus intermittent, oral versus parenteral), comparisons with other agents, and their use in combination with other agents.
Diphosphonates↗
How to get the most out of bone densitometry. Results can help assess fracture risk and guide therapy.
Bone densitometry has well-established usefulness in assessing fracture risk. Anyone with a condition that might reduce bone mass or accelerate bone loss should undergo testing, as should postmenopausal women and perimenopausal women who are undecided about starting estrogen replacement therapy. When stratifying a patient's risk of fracture, clinicians should consider not only BMD but also age, lifestyle, concurrent illness, and family history. Almost all patients with BMD in the osteoporotic range on densitometry should be considered for pharmacologic therapy, and so should many of those with values in the osteopenic range. Periodic retesting with bone densitometry is appropriate to monitor the progress of age-related bone loss and response to therapy. There are differences among skeletal sites used in BMD measurement, particularly regarding response to therapy. In addition, there are differences in calibration among densitometry machines, so whenever possible, serial studies should be done on the same machine and by the same technologist.
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Benign symmetric lipomatosis associated with protease inhibitors.
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Adult↗
Cyclical etidronate in the treatment of postmenopausal osteoporosis: efficacy and safety after seven years of treatment.
PURPOSE: To determine the efficacy and safety of cyclical etidronate for up to 7 years in the treatment of postmenopausal osteoporosis and to examine the effects of discontinuing treatment after 2 or 5 years of therapy. PATIENTS AND METHODS: Patients were randomized at entry into the original study in 1986 to blinded treatment for 2 years with either a calcium (placebo) or an intermittent cyclical etidronate regimen, which most patients continued for a third year. Following this phase of the study, patients were enrolled into an open-label, follow-up study (years 4 and 5), during which all patients received cyclical etidronate treatment. In the present double-blind study (years 6 and 7), patients were rerandomized to receive intermittent cyclical therapy with either etidronate or placebo; all patients received calcium. The treatment regimen consisted of 400 mg/day etidronate or placebo for 14 days, followed by 76 days of elemental calcium (500 mg/day); this cycle was repeated approximately 4 times in each year. Of the 193 patients who continued in years 6 and 7 of the study, 93 were randomized to receive cyclical etidronate and 100 were randomized to receive calcium only. For purposes of efficacy analyses, patients were categorized by their total years of cumulative etidronate treatment (7, 5, 4, or 2 years). There were 51, 46, 42, and 54 patients in the 7-, 5-, 4-, and 2-year groups, respectively. Annual assessments included lumbar spine bone mineral density (BMD), as measured by densitometry, and vertebral radiographs. RESULTS: The groups receiving cyclical etidronate during this 2-year study period (7- and 4-year groups) had statistically significant mean percent increases in spinal BMD of 1.8% and 2.2%, respectively (P < 0.05) at the week 104 observation time. The 5- and 2-year groups, which did not receive etidronate during this period, had mean values of 1.4% and 0.2%, respectively (not significant) at week 104. In the 7-, 5-, 4-, and 2-year groups, the increases in spinal BMD at the end of 7 years were 7.6%, 8.6%, 8.1%, and 3.9%, respectively; these values were statistically significant for all groups compared with original baseline (year 0) (P < 0.05). BMD of the femur and wrist was maintained throughout the 7-year period. The incidence and rate of vertebral fractures were lowest in patients with the longest exposure to etidronate. Etidronate was well tolerated during the study, with low incidences of gastrointestinal side effects and nonvertebral fractures. CONCLUSIONS: Long-term cyclical etidronate is a safe, effective, and well-tolerated treatment for postmenopausal osteoporosis. Bone mass is maintained for at least 2 years after treatment with etidronate is stopped; however, further gains in spinal bone mass are seen in patients who continue therapy.
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Introduction: management of osteoporosis, 1997.
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Animals↗
Osteoporosis: prevention, detection and treatment.
Osteoporosis is a common and costly condition that can cause disability or death. Bone density testing permits identification of individuals who are at high risk of fracture. Adequate calcium, vitamin D, and weight-bearing exercise are important, but pharmacologic intervention is indicated and effective for increasing bone mass and decreasing fracture risk.
Aged↗
Diabetic muscle infarction.
PURPOSE: To describe the clinical, histologic, and radiologic findings in patients with diabetic muscular infarction (DMI). MATERIALS AND METHODS: Descriptive case series of 3 patients with DMI and 22 previously reported cases (MEDLINE data base search) in the English literature are presented. RESULTS: Diabetic muscular infarction is usually seen in patients with long-standing insulin-dependent diabetes and multiple end-organ microvascular complications. Two-thirds of patients with DMI are women, with a mean age at presentation of 39 +/- 12 years. The typical clinical presentation includes abrupt onset of thigh pain and tenderness. There is a palpable, painful mass, with swelling and induration of the surrounding tissue without systemic symptoms or signs. The painful lesion persists for weeks, occasionally with exacerbations of symptoms, then spontaneously resolves over several weeks to months. Recurrent episodes are reported in half of the patients. Muscles commonly affected are the vastus lateralis, thigh adductors, and biceps femoris; but calf muscles may be involved as well. Active pathologic changes in the muscle are more sensitively evaluated with T2-weighted sequences on magnetic resonance (MR) imaging, which shows high intensity in involved muscle. Histologic features of DMI consist of large areas of muscle necrosis and edema. Regenerating muscle fibers and lymphocytic interstitial infiltration may be present. CONCLUSION: Diabetic muscular infarction is a rare complication of diabetes mellitus. In most patients, the diagnosis can be made when the characteristic clinical presentation is combined with a typical MR imaging results. Muscle biopsy can be helpful in establishing the diagnosis of DMI, but histologic findings are not specific. Awareness of this syndrome plus MR imaging as the first diagnostic test should lead to the correct diagnosis and shorter hospitalization.
Adult↗
Clinical utility of bone mass measurements in adults: consensus of an international panel. The Society for Clinical Densitometry.
Low bone mass predicts future fracture risk as well as high cholesterol or high blood pressure can predict the risk of heart disease or stroke. Prevention of the first fracture should be a clinical goal. In patients without fractures, osteopenia and osteoporosis can be diagnosed based on the extent of reduction in bone mass below mean peak bone mass of young healthy individuals. As bone mass decreases, fracture risk increases exponentially. Clinical situations in which an assessment of bone mass and fracture risk affects therapeutic decisions include estrogen deficiency, vertebral abnormalities, radiographic osteopenia, asymptomatic primary hyperparathyroidism, and long-term corticosteroid therapy. Serial measurements can also be used to monitor the effects of osteoporosis treatments. The appropriate technique and skeletal site for bone mass measurements should be chosen based on the patient's circumstances and the precision of measurement. A clinical interpretation can enhance the value of computer-generated bone mass measurement reports and improve decision making.
Absorptiometry, Photon↗
Introduction: osteoporosis 1996.
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Age Factors↗
Comparison of oral estrogens and estrogens plus androgen on bone mineral density, menopausal symptoms, and lipid-lipoprotein profiles in surgical menopause.
OBJECTIVE: To compare an oral estrogen-androgen combination with estrogens alone on bone, menopausal symptoms, and lipoprotein profiles in postmenopausal women. METHODS: Surgically menopausal women received oral esterified estrogens (1.25 mg), or esterified estrogens (1.25 mg) and methyltestosterone (2.5 mg) daily, for 2 years. Bone mineral density of the lumbar spine and hip, menopausal symptoms, lipoprotein profiles, and biochemical and hematologic indices were evaluated. RESULTS: Sixty-six patients were enrolled in the study. Both treatment regimens prevented bone loss at the spine and hip; combined estrogen-androgen therapy was associated with a significant increase in spinal bone mineral density compared with baseline (n = 24; mean score +/- standard error 3.4 +/- 1.2%, P < .01). In the estrogen group, high-density lipoprotein (HDL) cholesterol increased significantly and low-density lipoprotein cholesterol decreased significantly. Cholesterol, HDL cholesterol, and triglycerides decreased significantly in the estrogen-androgen group. Menopausal symptoms of somatic origin (hot flashes, vaginal dryness, and insomnia) were improved significantly by both treatments. Neither adverse hepatic effects nor significant safety or tolerance problems were reported in either group. CONCLUSION: Oral estrogen-androgen increased vertebral bone mineral density compared with pre-treatment values and relieved somatic symptoms. Safety indices, including lipoprotein levels, indicated that the combination was well tolerated over the 2 years of treatment.
Administration, Oral↗