PubMed · 15558708
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Ronald Jaffe. 2005. Curiouser and curiouser.. https://doi.org/10.1002/pbc.20136
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BACKGROUND: Patients with chronic kidney disease have significant abnormalities of bone remodelling and calcium homeostasis and are at increased risk of fracture. The fracture risk for a kidney transplant recipient is four times that of the general population and higher than that for a patient on dialysis. Trials reporting the use of bisphosphonates, vitamin D analogues, calcitonin, and hormone replacement therapy to treat bone disease following engraftment exist. OBJECTIVES: To evaluate the use of interventions for the treatment of bone disease following kidney transplantation. SEARCH STRATEGY: The Cochrane CENTRAL Register of Controlled Trials (The Cochrane Library - Issue 3 2004), MEDLINE (1966 to August 2004), EMBASE (1980- August 2004) and reference lists were searched without language restriction. SELECTION CRITERIA: Randomised trials of treatment of bone disease following kidney transplantation were included. Trials of recipients of any transplant other than a kidney transplant including trials of kidney-pancreas transplants were excluded. DATA COLLECTION AND ANALYSIS: Two authors assessed independently trial quality and extracted data. Statistical analyses were performed using the random effects model and the results expressed as relative risk (RR) with 95% confidence intervals (CI) for dichotomous variables. For continuous variables the weighted mean difference (WMD) and its 95% CI was used. MAIN RESULTS: Twenty-three eligible trials (1,209 patients) were identified. Seven trials compared more than two interventions. Nineteen trials compared active treatment with placebo, five vitamin D analogue and calcium, six vitamin D analogue alone, twelve bisphosphonates, and four nasal calcitonin. Eight trials compared two active treatments, one 17-beta oestradiol and medroxyprogesterone versus vitamin D analogue, five bisphosphonate versus vitamin D analogue, two vitamin D analogue and calcium versus calcium and one bisphosphonate versus calcitonin. Methodological quality was suboptimal. There were no significant differences between any treatment group for risk of fracture. Bisphosphonate, administered by any route, vitamin D analogue and calcitonin all had a beneficial effect on the bone mineral density at the lumbar spine. Bisphosphonates and vitamin D analogue had a beneficial effect on the bone mineral density at the femoral neck. Few or no data were available for combined hormone replacement, testosterone, selective oestrogen receptor modulators, fluoride or anabolic steroids. All-cause mortality and drug-related toxicity were reported infrequently and there was no statistical difference between treatment groups. AUTHORS' CONCLUSIONS: No benefit from any intervention known to reduce risk of fracture from bone disease could be demonstrated to reduce fracture incidence in kidney transplant recipients.
Osteoporosis, arthritis, and periodontal disease are common diseases of the skeleton, all of which could benefit from new therapeutic strategies, including targeted drug delivery. While bone is a rigid structure, it is not inert, with the cells of the skeleton being able to repair damage and respond to alterations in mechanical stimuli and various endocrine agents. Several important factors related to bone physiology that could influence the success of a pharmacological treatment include heterogeneity in bone remodeling activities throughout the skeleton, differences in blood supply and local vascularization, and the "blood-bone" barrier. The structural qualities of bone, especially the presence of hydroxyapatite crystals in the bone mineral and the established binding of certain molecules to this mineral phase, including tetracyclines, bisphosphonates, and other chelators, provide unique opportunities to treat skeletal diseases using targeted drug delivery. Additional opportunities exist in targeting sites with contrasting bone surface activities, including surfaces that are inactive, forming new bone or being resorbed. The ultimate key to developing new bone-targeted therapies is to understand and exploit the physiological characteristics at the desired target sites.