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Biomedical subjects

David Hosking

Publications and source records attributed to David Hosking.

12 recordsLinked to original sources
PubMed2007

Long-term control of bone turnover in Paget's disease with zoledronic acid and risedronate.

UNLABELLED: A single 5-mg infusion of zoledronic acid restores biochemical markers of bone turnover into the reference range in the majority of patients with Paget's disease and maintains biochemical remission for at least 2 years. This effect is largely independent of pretreatment disease activity and prior bisphosphonate therapy. INTRODUCTION: Zoledronic acid (ZOL) is a potent bisphosphonate that produces a rapid and complete control of the increased bone turnover of Paget's disease. Long-term control of disease activity is an important aim of treatment in the hope that this will reduce the risk of complications such as deformity, fracture, and degenerative joint disease. MATERIALS AND METHODS: This study compares the ability of ZOL 5 mg given as a 15-minute intravenous infusion with risedronate (RIS) 30 mg daily by mouth for 60 days to maintain long-term control of bone turnover. No bisphosphonate was given during the extension study. All patients (n = 296) who achieved a therapeutic response, defined as normalization or a >75% reduction in the total alkaline phosphatase (total ALP) excess above the midpoint of the reference range, were eligible for inclusion. RESULTS: ZOL maintained the mean level of total ALP at the middle of the reference range, whereas those treated with risedronate showed a linear increase in total ALP from the 6-month post-treatment time-point. Both treatments resulted in a linear relationship between the 6-month nadir and 24-month total ALP. The relationship for RIS was shifted upward, showing that for a given level of post-treatment biochemical activity, bone turnover increased with time. This was in contrast to the ZOL-treated patients where total ALP generally remained unchanged over this 18-month extension period. A similar pattern of response was seen with the other bone turnover markers. CONCLUSIONS: ZOL maintains bone turnover within the reference range over 24 months from the initiation of treatment. A reduction in the incidence and severity of long-term complications may require persistent normalization of bone turnover over many years, and this now seems a realistic possibility with ZOL.

Administration, Oral↗
PubMed2006

Esophageal transit of the weekly film-coated risedronate (Actonel) placebo tablet in subjects with Kyphosis.

Risedronate sodium is a pyridinyl bisphosphonate of proven effectiveness for the treatment and prevention of osteoporosis and Paget's disease of the bone. The aim of this study was to compare the esophageal transit and gastric emptying of the placebo film-coated risedronate tablet when taken with 50 or 120 mL of water in subjects with Kyphosis. A total of 23 patients with radiologically documented osteoporosis participated in a single-center, open-label, crossover gamma scintigraphy study. The mean esophageal transit times were 15.6 s (50 mL) and 12.0 s (120 mL) and the mean gastric emptying half-times were 20.5 min (50 mL) and 14.3 min (120 mL). There was no relationship between the degree of Kyphosis measured from lateral standing radiographs and the esophageal transit time. This study demonstrated that even when taken with a minimal volume of water the esophageal transit and gastric emptying of the film-coated 35 mg weekly risedronate placebo tablet was similar in kyphotic subjects to previously obtained results from healthy control subjects.

Administration, Oral↗
PubMed2006

Pharmacological therapy of Paget's and other metabolic bone diseases.

Paget's disease is a relatively common high-turnover metabolic bone disease that can serve as a model for osteoporosis and other metabolic bone diseases in investigation of therapeutic strategies to normalize bone turnover. Aims of treatment include rapid normalization of bone formation and resorption to prevent loss of mechanical integrity. Treatment will also reduce pain, while long-term maintenance of normal turnover may prevent long-term complications. Newer bisphosphonates have high antiresorptive potency and increased retention in bone, permitting a strategy of intermittent intravenous (IV) administration in achieving and maintaining normal bone turnover. In pivotal zoledronic acid Paget's disease trials, patients received a single 15-min IV infusion of zoledronic acid 5 mg (ZOL 5 mg) or risedronate 30 mg/day orally for 2 months. Treatment with ZOL 5 mg was associated with significant improvement in serum alkaline phosphatase, normalization in both the short and long term, and significant prolongation of biochemical therapeutic response in long-term follow-up. No changes in serum creatinine levels were observed with either treatment, and no clinically significant renal abnormalities were reported. Intermittent IV administration of potent bisphosphonates constitutes an intriguing strategy for treatment of Paget's disease and other metabolic bone diseases.

Bone Density Conservation Agents↗
PubMed2006

Alendronic acid produces greater effects than risedronic acid on bone density and turnover in postmenopausal women with osteoporosis : results of FACTS -international.

BACKGROUND: The objective of the study was to evaluate the effects of alendronic acid once weekly relative to risedronic acid once weekly on bone mineral density (BMD), markers of bone turnover and tolerability in the treatment of osteoporosis in postmenopausal women. METHODS: This was a randomised, double-masked, double-dummy multicentre international study (75 centres in 27 countries in Europe, the Americas and Asia-Pacific). A total of 1303 women were screened and 936 with low bone density (T-score < or = -2.0 at the spine, hip trochanter, total hip or femoral neck) were randomised; 91% (n = 854) completed the study. Patients were randomised to treatment with either active alendronic acid 70 mg weekly (Fosamax) and placebo identical to risedronic acid weekly or active risedronic acid 35 mg weekly (Actonel) and placebo identical to alendronic acid weekly for 12 months. The primary efficacy endpoint was the percentage change from baseline in hip trochanter BMD at 12 months. Secondary endpoints included the percentage change from baseline in lumbar spine, total hip and femoral neck BMD; biochemical markers of bone turnover (including serum bone-specific alkaline phosphatase [BSAP] and urinary type I collagen N-telopeptides [NTx]); and safety and tolerability as assessed by reporting of adverse experiences. RESULTS: Alendronic acid produced greater increases in BMD than did risedronic acid at 12 months at all sites measured. Mean percentage increases from baseline in hip trochanter BMD at month 12 were 3.56% and 2.71% in the alendronic acid and risedronic acid groups, respectively (treatment difference [95% CI]: 0.83% [0.22, 1.45; p = 0.008]). Mean percentage increases from baseline were greater with alendronic acid than risedronic acid at the lumbar spine, total hip and femoral neck BMD at month 12 (p = 0.002, p < 0.001, p = 0.039, respectively). Increases in BMD with alendronic acid compared with risedronic acid were also significantly greater at 6 months at the trochanter and total hip. There was a greater reduction in bone turnover with alendronic acid compared with risedronic acid: NTx decreased 58% with alendronic acid compared with 47% with risedronic acid at 12 months (p < 0.001); and BSAP decreased 45% with alendronic acid compared with 34% with risedronic acid at 12 months (p < 0.001). Overall tolerability and upper gastrointestinal tolerability were similar for both agents. CONCLUSIONS: Alendronic acid once weekly produced greater BMD increases at both hip and spine sites and greater reductions in bone turnover relative to risedronic acid once weekly. Both agents were well tolerated with no significant difference in upper gastrointestinal adverse experiences. Clinicians should consider these results when making treatment decisions for postmenopausal women with osteoporosis.

Aged↗
PubMed2005

Comparison of a single infusion of zoledronic acid with risedronate for Paget's disease.

BACKGROUND: The advent of bisphosphonates advanced therapy for Paget's disease, but more effective and convenient agents are needed to increase adherence. Zoledronic acid, a bisphosphonate administered as a single intravenous infusion, might meet these needs. METHODS: In two identical, randomized, double-blind, actively controlled trials of 6 months' duration, we compared one 15-minute infusion of 5 mg of zoledronic acid with 60 days of oral risedronate (30 mg per day). The primary efficacy end point was the rate of therapeutic response at six months, defined as a normalization of alkaline phosphatase levels or a reduction of at least 75 percent in the total alkaline phosphatase excess. The results of the studies were pooled. RESULTS: At six months, 96.0 percent of patients receiving zoledronic acid had a therapeutic response (169 of 176), as compared with 74.3 percent of patients receiving risedronate (127 of 171, P<0.001). Alkaline phosphatase levels normalized in 88.6 percent of patients in the zoledronic acid group and 57.9 percent of patients in the risedronate group (P<0.001). Zoledronic acid was associated with a shorter median time to a first therapeutic response (64 vs. 89 days, P<0.001). Higher response rates in the zoledronic acid group were consistent across all demographic, disease-severity, and treatment-history subgroups and with changes in other bone-turnover markers. The physical-component summary score of the Medical Outcomes Study 36-item Short-Form General Health Survey, a measure of the quality of life, increased significantly from baseline at both three and six months in the zoledronic acid group and differed significantly from those in the risedronate group at three months. Pain scores improved in both groups. During post-trial follow-up (median, 190 days), 21 of 82 patients in the risedronate group had a loss of therapeutic response, as compared with 1 of 113 patients in the zoledronic acid group (P<0.001). CONCLUSIONS: A single infusion of zoledronic acid produces more rapid, more complete, and more sustained responses in Paget's disease than does daily treatment with risedronate.

Administration, Oral↗
PubMed2005

Self-administered subcutaneous fluid infusion at home in the management of fluid depletion and hypomagnesaemia in gastro-intestinal disease.

BACKGROUND AND AIMS: In short bowel fistula and some other gastrointestinal (GI) diseases, salt, water and magnesium (Mg) balance may continue negative despite oral treatment, even in patients with adequate nutritional status. This study describes the use of self-administered subcutaneous fluid infusions (HSCF) to treat this problem. PATIENTS & METHODS: HSCF was administered to patients with GI failure and adequate macro-nutrient status (BMI) when GI salt, water and magnesium balance continued negative despite optimal diet, drug and supplemental treatment. Mg depletion was confirmed using the Mg load test. Patients were taught to self-administer 0.5-1.0 l 0.9% saline +/-0.5 l 5% dextrose +/-2-4 mmol MgSO4 subcutaneously by gravity drip during 6-12 h overnight, 3-7 days/week. Water and Na balance were assessed (weight, serum creatinine, urea, Na) at baseline and at 1 and 3 months of treatment, but also monitored carefully during the first few days of treatment. Serum Mg was measured at baseline and at 2 and 4 weeks. RESULTS: In 10 patients (mean age 65.3+/-13.5 years) Na and water balance was rapidly restored. At baseline, 1 and 3 months, serum biochemical results were: Eight patients received 8-28 mmol MgSO4/week in the infused fluid. Serum Mg [0.7-1.0 mmol] at baseline, 2 and 4 weeks was 0.49+/-0.06, 0.79+/-0.18, 0.83+/-0.10 mmol/l (P=0.002). Tolerance was good; transient oedema developed in 2 patients, resolved by reducing infusion dose. No patient developed hypokalaemia. CONCLUSIONS: Subcutaneous self-administered fluid infusion at home (HSCF) is an easily managed, safe and effective method of restoring and maintaining water, salt and Mg balance in patients with large GI fluid losses but adequate macronutrient status, particularly in the frail or elderly in whom home parenteral nutrition may be difficult.

Aged↗
PubMed2004

Ten years' experience with alendronate for osteoporosis in postmenopausal women.

BACKGROUND: Antiresorptive agents are widely used to treat osteoporosis. We report the results of a multinational randomized, double-blind study, in which postmenopausal women with osteoporosis were treated with alendronate for up to 10 years. METHODS: The initial three-year phase of the study compared three daily doses of alendronate with placebo. Women in the original placebo group received alendronate in years 4 and 5 and then were discharged. Women in the original active-treatment groups continued to receive alendronate during the initial extension (years 4 and 5). In two further extensions (years 6 and 7, and 8 through 10), women who had received 5 mg or 10 mg of alendronate daily continued on the same treatment. Women in the discontinuation group received 20 mg of alendronate daily for two years and 5 mg daily in years 3, 4, and 5, followed by five years of placebo. Randomized group assignments and blinding were maintained throughout the 10 years. We report results for the 247 women who participated in all four phases of the study. RESULTS: Treatment with 10 mg of alendronate daily for 10 years produced mean increases in bone mineral density of 13.7 percent at the lumbar spine (95 percent confidence interval, 12.0 to 15.5 percent), 10.3 percent at the trochanter (95 percent confidence interval, 8.1 to 12.4 percent), 5.4 percent at the femoral neck (95 percent confidence interval, 3.5 to 7.4 percent), and 6.7 percent at the total proximal femur (95 percent confidence interval, 4.4 to 9.1 percent) as compared with base-line values; smaller gains occurred in the group given 5 mg daily. The discontinuation of alendronate resulted in a gradual loss of effect, as measured by bone density and biochemical markers of bone remodeling. Safety data, including fractures and stature, did not suggest that prolonged treatment resulted in any loss of benefit. CONCLUSIONS: The therapeutic effects of alendronate were sustained, and the drug was well tolerated over a 10-year period. The discontinuation of alendronate resulted in the gradual loss of its effects.

Aged↗
PubMed2004

Putting evidence-based medicine into clinical practice: comparing anti-resorptive agents for the treatment of osteoporosis.

OBJECTIVE: To compare the effectiveness of antiresorptive agents in reducing the risk of vertebral and non-vertebral fractures using data from published meta-analyses and the technique of adjusted indirect comparisons. RESEARCH DESIGN AND METHODS: Pairs of agents were compared by adjusted indirect comparison of 0.56 [0.40, 0.78], respectively) in reducing the their effects relative to a common comparator (placebo) using meta-analyses published by The Osteoporosis Methodology Group and The Osteoporosis Research Advisory Group. RESULTS: Adjusted indirect comparisons identified only one pair of agents that had significantly different effects on vertebral fracture incidence: alendronate was 34% more effective than calcitonin (Relative Risk: 0.66, 95% Confidence Interval: 0.48-0.90). Alendronate was significantly more effective than risedronate, calcitonin, estrogen, etidronate, and raloxifene (Relative Risks: 0.70 [0.49, 0.99], 0.64 [0.42, 0.98], 0.59 [0.41, 0.84], 0.52 [0.32, 0.82], and incidence of non-vertebral fractures. No other significant pairwise differences were observed. CONCLUSIONS: The results suggest that there are differences in anti-fracture efficacy among antiresorptive agents, particularly for non-vertebral fractures. Direct head-to-head comparisons would be needed to confirm these findings but are unlikely to be conducted.

Alendronate↗
PubMed2004

Hyperparathyroidism in the elderly patient.

Primary hyperparathyroidism is a common metabolic bone disease and currently presents a significant management dilemma. Most of the patients have few relevant symptoms and surgical parathyroidectomy offers the prospect of cure with freedom from the risk of long-term complications or the need for a follow-up. However, there is a natural reluctance to subject elderly patients to an operation where the balance of advantage is less clear. Advances in parathyroid imaging resulting in a greater use of targeted or focused parathyroidectomy has opened the way for the inclusion of less fit patients into the potentially operable category. However, there is still debate about whether these newer imaging techniques are sufficiently helpful and cost effective to warrant their use in all patients who may need parathyroid surgery. This has stimulated a debate about the indications for parathyroidectomy in the elderly and whether advances in medical therapy, which offset the end organ effects of excess parathyroid hormone, are of sufficient benefit to counteract this trend towards greater surgical intervention. These considerations mean that it is not possible to consider the merits of pharmacological therapy for primary hyperparathyroidism without reviewing the relative merits of minimally invasive and conventional surgery.

Aged↗
PubMed2003

Comparison of change in bone resorption and bone mineral density with once-weekly alendronate and daily risedronate: a randomised, placebo-controlled study.

OBJECTIVE: To compare the effects of alendronate (ALN) 70 mg once weekly (OW) and risedronate (RIS) 5 mg daily between-meal dosing on biochemical markers of bone turnover and bone mineral density (BMD) in postmenopausal women with osteoporosis. RESEARCH DESIGN AND METHODS: This was a 3-month, randomised, double-blind, placebo-controlled study with a double-blind extension to 12 months. The study enrolled 549 postmenopausal women (ALN 219, RIS 222 and placebo (PBO) 108) who were > or =60 years of age at outpatient centres. MAIN OUTCOME MEASURES: The primary endpoint was reduction in urine N-telopeptides of type 1 collagen (NTx) corrected for creatinine level at 3 months. Secondary parameters included change in BMD at the spine and hip at 6 and 12 months, NTx at 1, 6 and 12 months, and serum bone-specific alkaline phosphatase (BSAP) at 1, 3, 6 and 12 months. Adverse experiences (AEs) were recorded throughout the study for an assessment of treatment safety profiles and tolerability. RESULTS: Over 3 months, ALN produced a significantly greater mean reduction in urine NTx than did RIS (-52% vs -32%, p < 0.001), which was maintained at 12 months. ALN produced a significantly greater mean BMD increase than did RIS at 6 months, and it was maintained at 12 months at the lumbar spine (4.8% vs 2.8%, p < 0.001) and total hip (2.7% vs 0.9%, p < 0.001), as well as at the trochanter and femoral neck. Significant reductions in BSAP with ALN compared to RIS were maintained over the 12 months of treatment. Study size did not allow for meaningful assessment of differences in fracture rates. Tolerability was generally similar between ALN, RIS and PBO, and the incidence of upper GI AEs causing discontinuation and oesophageal AEs was similar in the ALN and RIS groups. CONCLUSION: In this study, ALN 70 mg OW produced a 50% greater reduction in bone resorption as measured by urine NTx and significantly greater increases in lumbar spine and hip BMD than did RIS 5 mg daily. The treatments had similar safety profiles and were generally well-tolerated. Additional studies are needed comparing OW ALN with OW RIS, which became available after the commencement of the present study.

Aged↗
PubMed2003

A comparison of calcaneal dual-energy X-ray absorptiometry and calcaneal ultrasound for predicting the diagnosis of osteoporosis from hip and spine bone densitometry.

Peripheral densitometry is increasingly being used in the management of osteoporosis, but the optimal diagnostic thresholds have not been defined. The aim of this study was to determine the optimal T-score for peripheral dual-energy X-ray absorptiometry (pDXA) of the heel using a GE Lunar PIXI and quantitative ultrasound (QUS) of the heel using a GE Lunar Achilles Plus when compared with dual-energy X-ray absorptiometry (DXA) of central sites (spine, femoral neck, or total hip). Ninety-nine women (mean age 69 +/- 8, range 33-86 yr) referred from the metabolic bone clinic were studied. The optimal T-score for pDXA from ROC analysis was -1.7 and for QUS was -2.5. The pDXA T-score that defined the same prevalence of osteoporosis at any central site was also -1.7 and for QUS was -2.4. These results are similar to the manufacturer's recommendations. There is no significant difference in performance between the PIXI and QUS.

Absorptiometry, Photon↗