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Review Tolerability of different dosing regimens of bisphosphonates for the treatment of osteoporosis and malignant bone disease. 2006
Bobba RS, Beattie K, Parkinson B, Kumbhare D, Adachi JD. · Division of Rheumatology, McMaster University, Hamilton, Ontario, Canada. · Drug Saf. · Pubmed #17147460 No free full text.
Abstract: Bisphosphonates are the primary pharmacological agents used for the management of osteoporosis and hypercalcaemia of malignant bone disease. The efficacy of these agents in these two conditions has been demonstrated in many well designed trials published over the past 2 decades. The variety of bisphosphonates currently available to us provides a wide range of tolerability and dosing profiles thus necessitating a thorough comparison of the most recent oral and intravenous bisphosphonates to differentiate the clinical context in which they should be used. Despite the fact that bisphosphonates are generally well accepted, their tolerability is dependent on complications which encompass gastrointestinal (GI) and renal toxicity. Other adverse events include osteonecrosis of the jaw, arthralgias, flu-like symptoms and uveitis. Studies have shown that various dosing regimens are able to modulate these rates of toxicity. To maximise tolerability, the direction of future therapy will likely fall into a pattern of decreasing the frequency of administration of bisphosphonates, whether it is oral or intravenous formulations, thus improving patient adherence. To review the literature on different dosing regimens of various bisphosphonates and their associated tolerability, we searched MEDLINE for articles from 1975 to 2006. Oral bisphosphonates, in particular alendronate and risedronate, have been systematically evaluated with regards to GI toxicity. Overall tolerability with these oral formulations has found GI toxicity to be the primary adverse event of interest. Both alendronate and risedronate have been found to have similar rates of GI toxicity when compared with placebo. Mounting evidence has developed validating the use of intravenous ibandronate and zoledronic acid for the purpose of treating hypercalcaemia secondary to malignancy. Unique to all other bisphosphonates, ibandronate also has an oral form which has a similar GI-toxicity profile to placebo. In addition, no significant differences in renal toxicity have been observed between those receiving intravenous ibandronate compared with placebo. Because of its potency and mode of administration, zoledronic acid has been widely accepted for the treatment of hypercalcaemia secondary to malignancy. However, a decrease in renal function, albeit rare, remains a significant complication of zoledronic acid; therefore, regular renal monitoring is recommended.
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Article Validity of serum creatine kinase as a measure of muscle injury produced by lumbar surgery. 2008
Kumbhare D, Parkinson W, Dunlop B. · McMaster Medical Rehabilitation, Department of Medicine, McMaster University, Ontario, Canada. · J Spinal Disord Tech. · Pubmed #18418137 No free full text.
Abstract: BACKGROUND AND PURPOSE: Serum creatine kinase (CK) concentrations have historically been used to investigate muscle disease and serious muscle damage, and there is a growing interest in the potential for a biochemical approach to quantifying skeletal muscle injury occurring in orthopedic surgeries and spinal injuries. The wide availability of CK measurement could foster spinal muscle injury research. However, measurement validity has never been systematically demonstrated in clinical settings. In this study, the validity of serum CK concentration elevation as an index of muscle injury was investigated using lumbar decompression surgery (LDS) as a model. SUBJECTS AND METHODS: Blood samples were obtained from 18 research volunteers drawn from the clinical population undergoing LDS. A baseline sample was taken in the preoperative waiting area. Each subject's highest CK concentration between 12 and 48 hours after surgery was used as the biochemical injury response. The surface area of muscle isolated (incision lengthxdepth) and strained by retraction was obtained for concurrent validity testing against biochemical measurement. RESULTS: The correlation between highest total CK concentration and muscle surface area was moderate (r=0.60) and significant (P<0.01). Correlations between surface area and CK at specific time points, revealed minimal loss of association at 12 hours (r=0.57) and 24 hours (r=0.58), but weaker correlations at 6 hours (r=0.45) and 48 hours (r=0.28) after injury. Analyses for proportions of each isoenzyme making up the total CK revealed that baseline and peak CK consisted almost exclusively of skeletal muscle CK (CK-MM), with minimal representation by heart muscle (CK-MB), and brain (CK-BB). CONCLUSIONS: The findings provide support for the validity of serum CK measurement as an index of skeletal muscle injury caused by LDS, and demonstrate that LDS provides a useful model for measurement testing and development studies.
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Article Prevalence of vertebral fractures among patients with chronic obstructive pulmonary disease in Canada. 2003
Papaioannou A, Parkinson W, Ferko N, Probyn L, Ioannidis G, Jurriaans E, Cox G, Cook RJ, Kumbhare D, Adachi JD. · Department of Medicine, McMaster University, Hamilton, Ontario, Canada. · Osteoporos Int. · Pubmed #14551675 No free full text.
Abstract: PURPOSE: Patients with chronic obstructive pulmonary disease (COPD) may be at higher risk for osteoporosis. The primary objective of this case-control study was to determine the prevalence of vertebral fractures among patients with COPD admitted to acute care compared with a gender- and age-matched control group. SUBJECTS AND METHODS: Subjects were identified by chart reviews from an acute care hospital in Hamilton, Ontario, in 1999, including patients who were over 50 years old. In total, 127 patients with ICD-9 codes specifying COPD were randomly selected and compared with 127 gender- and age-matched controls. Chest radiographs were interpreted by two radiologists who defined and graded vertebral fractures using Genant's method. Medications taken, or prescribed at discharge, were recorded from charts. RESULTS: The overall prevalence of at least one vertebral fracture was found to be 34/127 (26.8%) in the COPD patients compared with 30/127 (23.6%) in the controls ( p=0.556). A significantly greater proportion of COPD patients had at least one severe vertebral fracture (OR=3.75, 95% CI 1.24 to 11.3). Review of hospital chest X-ray reports indicated that only 12 of 64 (18.8%) patients with vertebral fractures identified by the study radiologists actually had a vertebral fracture noted in the report. The proportion of COPD patients with vertebral fractures who were discharged on osteoporosis therapy was 5/27 (18.5%). There was a suggestion of lower lung function, as measured by forced vital capacity (FVC%), in patients with severe vertebral fractures ( p=0.067). CONCLUSIONS: These data indicate that: (1) There is an increased proportion of COPD patients with severe vertebral fracture, and (2) Documentation and treatment of osteoporosis in acute care COPD patients is low. Therefore, there is a need to target this high-risk group for osteoporosis screening and potential clinical management.
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