Do Beta Blockers Decrease Fracture Risk?
This population-based study explored the association between beta blocker use (with or without concomitant thiazides) and fracture risk in men and women aged 30-79 years. Data from the U.K.-based General Practice Research Database identified all patients diagnosed with a fracture in the computerized medical record between January 1993 and December 1999. Patients with medical disorders that affect bone metabolism (e.g., osteoporosis, alcoholism, and most cancers), as well as patients who used bisphosphonates, were excluded. Controls were persons from the same database, randomly selected, matched for age and sex, and with the same exclusion criteria as the study patients.
Patients were classified as current users of beta blockers (last prescription 1 to 59 days before the index date [date of fracture]), as recent users (last prescription recorded 60 to 119 days before the index date), or past users (last prescription recorded at least 120 days before the index date). All others were classified as nonusers. The study criteria identified 30,601 individuals with fractures and 120,819 matched controls.
Results support the evidence that current use of beta blockers is associated with a statistically significant decrease in fracture risk for both men and women. This risk reduction was apparent in users of three or more prescriptions; one prescription corresponded to 1 to 3 months of drug therapy.
The study found no evidence of altered fracture risk for users of calcium channel blockers. There was some suggestion that long-term use of ACE inhibitors might possibly reduce fracture risk.
Schlienger, R. G., Kraenzlin, M. E., Jick, S. S., & Meier, C. R. (2004). Use of beta blockers and risk of fractures. Journal of the American Medical Association, 292, 1326-1332.
Fracture Risk After Androgen Deprivation for Prostate Cancer
Androgen-deprivation therapy in the form of gonadotropin-releasing hormone antagonists is being used increasingly in men with localized prostate cancer (cancer confined to the prostate), as well as in men with increased prostate-specific antigen (PSA) after prostatectomy. To date, no survival benefit has been demonstrated for this group of patients as it has been for those with locally advanced disease when combined with radiation.
Rapid loss of bone mineral density (BMD) occurs within the first 6 months of androgen-deprivation therapy. Previously, small numbers and lack of a control group have limited fracture risk assessment associated with this treatment. This study used the linked databases of the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) program and Medicare to assess fracture risk associated with androgen deprivation in the form of orchiectomy or treatment with gonadotropin-releasing hormone agonists.
Data were retrieved on all men 66 years and older who had a first diagnosis of prostate cancer from 1992-1997. Comparisons were limited to men who received at least one dose of a gonadotropin-releasing hormone agonist or underwent orchiectomy within 6 months after the diagnosis was made with those who received neither type of treatment at any time after diagnosis. Overall, data were available for a total of 50,613 patients for the primary sample with follow-up through 2001.
Primary outcomes were any fracture and fracture resulting in hospitalization. Secondary outcomes were a diagnosis of osteoporosis and fractures at specific sites.
Use of androgen-deprivation treatment increased with increasing age, stage of cancer at diagnosis, grade of prostate cancer, and the presence of coexisting conditions. Additionally, there was an increase in the use of androgen-deprivation therapy during the period 1992-1997.
The relative risk of fracture occurrence or a fracture that resulted in hospitalization increased steadily with the increasing number of doses of a gonadotropin-releasing hormone agonist received during the first year after diagnosis. There were no statistically significant interactions between cancer stage or race or ethnic group and androgen deprivation. Older age and more advanced stages of cancer are confounding variables, which may account for fracture risk related to androgen deprivation. Also, patients who are about to receive this treatment may already have decreased BMD.
The study did not exclude fractures related to bone metastases. However, fracture risk was not reduced when the analysis was restricted to patients with early stage cancer who would be less likely to have bone metastases.
This study has two important implications. First, androgen-deprivation therapy is not benign. However, there is no evidence from clinical trials of a survival benefit for patients who receive this therapy. Second, trials of interventions to lower fracture risk among patients with prostate cancer are needed.
Men with prostate cancer being treated with androgen deprivation should have BMD monitored and should begin bisphosphonate therapy if osteoporosis develops or a fracture occurs. Further study is needed to assess the efficacy and cost effectiveness of bisphosphonate therapy to reduce fracture risk in men receiving androgen-deprivation therapy.
Shahinian, V. B., Kuo, Y., Freeman, J. L., & Goodwin, J. S. (2005). Risk of fracture after androgen deprivation for prostate cancer. New England Journal of Medicine, 352, 154-163.
Pain in Children With Cerebral Palsy
Current literature indicates that pain is a common experience for children with cerebral palsy (CP) but has been understudied in this population. Medical advances have resulted in increasing numbers of children living with disabilities. The interventions often used to improve motor control and function, modify deformities, reduce pain, and enhance quality of life can actually cause pain and discomfort. This article synthesizes the current literature on issues related to the experience of pain in children with CP.
CP represents a range of nonprogressive motor impairments that are identified at birth or in early childhood. CP is the leading cause of childhood physical disability in developed countries, with more than 10,000 infants and children diagnosed each year in the United States alone.
Pain in children is a relatively new area of research, and only recently has pain in adults with CP been researched. Results suggest that pain is common in patients with CP, with 67-84% of participants reporting chronic pain and 18-56% reporting daily pain in a range of studies. The largest group of patients referred to a pediatric multidisciplinary pain clinic in Australia were children with CP or spasticity. Research concerning pain in children with CP has emphasized parent or healthcare professional report, which may or may not accurately reflect the child's experience.
Pain is caused by surgery, procedures such as Botox injections, gastroesophageal reflux, orthopaedic and neuromuscular conditions, and rehabilitative interventions. Despite attention given to postoperative pain management in children with CP, little has been done to examine nonpharmacologic interventions or explore the experience of pain from the child's perspective.
Immobility, spasticity, and congenital deformity may contribute to painful orthopaedic conditions. Although the mechanism of spasticity-related pain is not well understood, pain may be associated with spasticity, as well as the resulting impairment and deformity. Children with CP often have a limited range of available functional movement and may develop overuse syndromes, nerve entrapments, radiculopathies, and myelopathies.
Chronic shortening and misalignment of muscles as a result of spasticity or restricted movement may lead to contractures, another potentially painful problem. Unfortunately, rehabilitative interventions, such as range of motion, stretching, and bracing, can produce pain as well.
Little research exists on pain assessment in children with CP. Motor, cognitive, and communication impairments complicate pain assessment and should be considered when choosing instruments to evaluate pain. Because pain and anxiety are difficult to separate in the clinical setting, the term "behavioral distress" is often used to capture the verbal, behavioral, and physiologic indications of the inseparable elements of pain and anxiety. Future research should explore not only the temporal descriptors and physiologic markers of pain in children with CP (e.g., intensity, frequency, duration) but also the functional effect of pain in terms of activities of daily living, quality of life, socialization, and psychologic ramifications.
McKearnan, K. A., Kieckhefer, G. M., Engel, J. M., Jensen, M. P., & Lab-yak, S. (2004). Pain in children with cerebral palsy: A review. Journal of Neuroscience Nursing 36:252-259.
Osteoporosis and the Statin Agents
Restoring balance between bone loss and formation is the key to preventing osteoporosis, the most common bone disorder in humans. This article reviews the data on statins and their effect on osteoporosis.
Statins decrease hepatic cholesterol synthesis by blocking the mevalonate pathway as well as by inhibiting 3-hydroxy-3-glutaryl-coenzyme A (HMG-CoA) in the liver. Statins also may inhibit osteoclast function by interfering with formation of cellular proteins.
Several clinical studies have investigated the relationship between statins and fractures. Three studies showed that current statin use was associated with decreased risk for nonpathologic fractures. However, two other observational studies showed no such association.
More recently, a meta-analysis of four large prospective studies-the Study of Osteoporotic Fractures (SOF), the Fracture Intervention Trial (FIT), the Heart and Estrogen/Progestin Replacement Study (HERS), and the Rotterdam Study-was performed. The data from these studies were combined with data from four other observational studies. The meta-analysis suggested that statins may prevent osteoporotic fractures. However, fracture risk was not reduced in women taking nonstatin lipid-lowering agents. These data supported a beneficial effect of statins on the skeleton.
Review of two placebo-controlled trials with cardiovascular endpoints did not document a protective effect on bone. Finally, authors of the Women's Health Initiative reviewed data on hip, lower arm, and wrist fractures among statin users and nonusers for almost 4 years. Bone density levels did not differ statistically between statin users and nonusers. The authors concluded that statin use did not improve fracture risk or bone mineral density and that evidence does not support the use of statins to prevent or treat osteoporosis.
Snyder, T. E. (2004). Osteoporosis and the statin agents. The Female Patient, 29(7), 9-16.