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Biomedical subjects

Nelson B Watts

Publications and source records attributed to Nelson B Watts.

17 recordsLinked to original sources
PubMed2003

Use of matched historical controls to evaluate the anti-fracture efficacy of once-a-week risedronate.

Placebo controls are essential to assess anti-fracture efficacy of new osteoporosis therapies, but inclusion of a placebo arm in a subsequent clinical trial may be limited by practical or ethical considerations; in these cases, use of an historical control may be appropriate. A recent active-controlled study of risedronate 35 mg once a week demonstrated that this regimen produces increases in bone mineral density (BMD) that are comparable to those seen with the risedronate 5 mg daily dose, which has proven anti-fracture efficacy. To assess the anti-fracture efficacy of this new regimen, we have analyzed the fracture data collected in an active controlled study of risedronate dosing regimens (the Once-a-Week study) using matched historical control data from previous placebo-controlled trials. Women in the Once-a-Week study were matched for age, years since menopause, BMD, and prevalent vertebral fracture status, with placebo patients in the Vertebral Efficacy of Risedronate Therapy (VERT) trials forming an historical placebo group. We also constructed an historical active treatment group from the 5 mg daily arm of the VERT trials for comparison with the 5 mg daily and 35 mg once weekly treatment groups in the Once-a-Week study. Data were obtained from the risedronate 5 mg daily group (n=480) and 35 mg once-a-week group (n=485) in the Once-a-Week study and historical control groups representing daily placebo patients (n=114, matched from 993) and risedronate 5 mg daily patients (n=120; matched from 990) in the VERT studies. Patients received calcium supplementation (1000 mg daily); vitamin D was given if baseline serum 25-hydroxyvitamin D levels were low. Over 1 year, new vertebral fracture risk in the 35 mg once-a-week group was reduced by 77% relative to the historical placebo group (1.2% versus 5.0%; RR 0.23; 95% CI, 0.54 to 0.91, P=0.018), similar to the 1-year risk reduction observed in the VERT trials of risedronate 5 mg daily (61-65%). The incidence of new vertebral fractures in the three active treatment groups was similar: 1.7% in the historical risedronate 5 mg group, 1.5% in the risedronate 5 mg daily group from the Once-a-Week study, and 1.2% in the 35 mg once-a-week group. Risedronate 35 mg once a week appears as effective as the 5 mg daily dose in reducing the risk of new vertebral fractures in the first year of treatment. The use of appropriate historical control data provides an approach to the assessment of fracture effects in osteoporosis trials for which placebo-controlled data are not available.

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PubMed2003

Bisphosphonate treatment of osteoporosis.

Bisphosphonates represent the agents of choice for most patients with osteoporosis. They are the best studied of all agents for the prevention of bone loss and reduction in fractures. They increase BMD, primarily at the lumbar spine, but also at the proximal femur. In patients who have established osteoporosis, bisphosphonates reduce the risk of vertebral fractures, and are the only agents in prospective trials to reduce the risk of hip fractures and other nonvertebral fractures. Bisphosphonates reduce the risk of fracture quickly. The risk of radiographic vertebral deformities is reduced after 1 year of treatment with risedronate [68]. The risk of clinical vertebral fractures is reduced after 1 year of treatment with alendronate [69] and just 6 months' treatment with risedronate [157]. The antifracture effect of risedronate has been shown to continue through 5 years of treatment [158]. Alendronate and risedronate are approved by the FDA for prevention of bone loss in recently menopausal women, for treatment of postmenopausal osteoporosis, and for prevention (risedronate) and treatment (alendronate and risedronate) of glucocorticoid-induced osteoporosis. Alendronate is also approved for treatment of osteoporosis in men. Other bisphosphonates (etidronate for oral use, pamidronate and zoledronate for intravenous infusion) are also available and can be used off label for patients who cannot tolerate approved agents. Although bisphosphonates combined with estrogen or raloxifene produce greater gains in bone mass compared with single-agent treatment, the use of two antiresorptive agents in combination cannot be recommended because the benefit on fracture risk has not been demonstrated and because of increased cost and side effects.

Bone Density↗
PubMed2003

Position Development Conference.

In a series of three published articles, the International Society for Clinical Densitometry has recorded the findings reached by an expert panel at the ISCD Position Development Conference held in July 2001. The key elements of those papers have been reviewed in this executive summary. It should be emphasized that the ISCD recommendations are not meant to serve as rigid guidelines or to replace clinical judgment. The recommendations will be reviewed and updated periodically as more data become available. A second Position Development Conference will be held in July 2003 in Cincinnati, OH. For information, visit the ISCD web site: http://www.iscd.org/.

Absorptiometry, Photon↗
PubMed2003

Risedronate prevents new vertebral fractures in postmenopausal women at high risk.

Independent risk factors for fracture include advanced age, preexisting fractures, and low bone mineral density. Rised-ronate has been shown in several large trials to be safe and effective for patients with osteoporosis, but its effects in populations at high risk are not well characterized. To determine the effect of risedronate on vertebral fracture in high-risk subjects, we pooled data from two randomized, double-blind studies [Vertebral Efficacy with Risedronate Therapy (VERT) Multinational (VERT-MN) and VERT-North America (VERT-NA)] in 3684 postmenopausal osteoporotic women treated with placebo or risedronate 2.5 or 5 mg/d and analyzed fracture risk in subgroups of subjects at high risk for fracture due to greater age or more prevalent fractures (vs. median for overall study population), or lower bone mineral density (T-score, -2.5 or less). Fractures were diagnosed by quantitative and semiquantitative assessment of radiographs at baseline and 1 yr. In the overall population, treatment for 1 yr with risedronate 5 mg/d reduced the risk of new vertebral fractures by 62% vs. control (relative risk, 0.38; 95% confidence interval, 0.25, 0.56; P < 0.001) and of multiple new vertebral fractures by 90% vs. control (relative risk, 0.10; 95% confidence interval, 0.04, 0.26; P < 0.001). Consistent risk reductions were observed at 1 yr in the risedronate-treated high-risk subgroups. Significant reduction in fracture risk after 1 yr is an important benefit in patients at high risk for fracture because, without treatment, these patients are likely to sustain new fractures in the near term.

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PubMed2002

Diagnosis and management of vertebral fractures in elderly adults.

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.

Age Distribution↗
PubMed2002

Localisation of mesenchymal tumours by somatostatin receptor imaging.

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.

Bone Neoplasms↗
PubMed2002

Combination therapy for postmenopausal osteoporosis.

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.

Aged↗
PubMed2002

Executive summary International Society for Clinical Densitometry position development conference Denver, Colorado July 20-22, 2001.

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.

Bone Density↗
PubMed2002

Position statements of the International Society for Clinical Densitometry: methodology.

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.

Bone Density↗
PubMed2002

Assessment and recommendations on factors contributing to preanalytical variability of urinary pyridinoline and deoxypyridinoline.

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.

Amino Acids↗
PubMed2002

Therapies to improve bone mineral density and reduce the risk of fracture: clinical trial results.

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.

Aged↗