Calcium Supplementation in Postmenopausal Women

CHERYL A. FLYNN, M.D., M.S., State University of New York Upstate Medical University, Syracuse, New York

The Cochrane Abstract below is a summary of a review from the Cochrane Library. It is accompanied by an interpretation that will help clinicians put evidence into practice. Cheryl A. Flynn, M.D., M.S., presents a clinical scenario and question based on the Cochrane Abstract, along with the evidence-based answer and a full critique of the abstract.

This clinical content conforms to AAFP criteria for evidence-based continuing medical education (EB CME). EB CME is clinical content presented with practice recommendations supported by evidence that has been systematically reviewed by an AAFP-approved source. The practice recommendations in this activity are available online at http://www.cochrane.org/cochrane/revabstr/ab004526.htm.

Clinical Scenario

A 53-year-old woman who is one year postmenopausal comes in for a routine examination. She asks about taking supplemental calcium to prevent osteoporosis.

Clinical Question

Should we recommend calcium supplementation for postmenopausal women?

Evidence-Based Answer

Calcium supplementation has a beneficial effect on bone density and may reduce vertebral fractures. It has no clear effect on nonvertebral fractures, although the number of patients studied may be too small to predict this outcome.

Cochrane Abstract Background. Although calcium is one of the simplest and least expensive strategies for preventing osteoporotic fractures, calcium supplementation is not without controversy. The U.S. Food and Drug Administration has permitted a bone health claim for calcium-rich foods, and a National Institutes of Health consensus statement notes that high calcium intake reduces the risk of osteoporosis. Objectives. To assess the effects of calcium supplementation on bone density and fractures in postmenopausal women. Search Strategy. The authors1 searched Cochrane Controlled Register, MEDLINE, and EMBASE up to 2001 and examined citations of relevant articles and proceedings of international meetings. Selection Criteria. Trials that randomized postmenopausal women to calcium supplementation or usual dietary calcium intake; followed patients for at least one year; and reported bone mineral density of the total body, vertebral spine, hip, or forearm or recorded the number of fractures were considered for inclusion in the study. Data Collection and Analysis. Three independent reviewers assessed the methodologic quality and extracted data from each trial. For each bone-density site (i.e., lumbar spine, total body, combined hip, and combined forearm), the authors calculated the weighted mean difference (WMD) in bone density between treatment and control groups using the percentage change from baseline. The authors constructed regression models in which the independent variables were year and dosage, and the dependent variable was the effect size. This regression was used to determine the years across which pooling was appropriate. Heterogeneity was asssessed. The authors calculated a risk ratio for each fracture analysis. Primary Results. Fifteen trials including 1,806 participants were included. Calcium was more effective than placebo in reducing rates of bone loss after two or more years of treatment. The pooled difference in percentage change from baseline was 2.05 percent for total body bone density (95 percent confidence interval [CI], 0.24 to 3.86), 1.66 percent for the lumbar spine at two years (95 percent CI, 0.92 to 2.39), 1.60 percent for the hip (95 percent CI, 0.78 to 2.41), and 1.91 percent for the distal radius (95 percent CI, 0.33 to 3.50). The relative risk (RR) for vertebral fractures was 0.79 (95 percent CI, 0.54 to 1.09), the RR for nonvertebral fractures was 0.86 (95 percent CI, 0.43 to 1.72). Reviewers' Conclusions. Calcium supplementation alone has a small positive effect on bone density. The data show a trend toward reduction in vertebral fractures, but it is unclear if calcium reduces the incidence of nonvertebral fractures. These summaries have been derived from Cochrane reviews published in the Cochrane Database of Systematic Reviews in The Cochrane Library. Their content has, as far as possible, been checked with the authors of the original reviews, but the summaries should not be regarded as an official product of the Cochrane Collaboration; minor editing changes have been made to the text (www.cochrane.org).

Practice Pointers

This was a well-conducted systematic review of calcium supplementation to increase bone density and reduce fracture risk in postmenopausal women. Although not statistically significant, there was a trend toward reduced vertebral fracture risk in postmenopausal women who take calcium. These data were consistent across trials. It is likely that the data did not reach statistical significance because of the small number of women enrolled in the studies (fewer than 600 total) and varying duration of follow-up (one to four years).

Results for secondary prevention of fractures also did not reach statistical significance. Results for bone mineral density, an intermediate outcome, showed less bone loss in women taking calcium than in those who received placebo. The decrease in bone loss was not statistically significant in women without osteoporosis, but it was statistically significant in women with osteoporosis.

Despite the limited data, calcium supplementation in postmenopausal women makes sense. The Institute for Clinical Systems Improvement guideline on diagnosis and treatment of osteoporosis2 recommends 1,200 mg of calcium per day for healthy women over age 50 and 1,500 mg per day for women who have osteoporosis, use glucocorticoids, or are pregnant, nursing, or older than 65. Other options for bone loss prevention include vitamin D, estrogen, bisphosphonates, and raloxifene. Bisphosphonates have the strongest evidence for prevention of fracture in women with osteoporosis.2 The 2000 National Institutes of Health consensus conference3 also recommends calcium supplementation in women who do not achieve recommended intake in their diet.

Based on the best available evidence, calcium supplementation seems like a worthwhile approach to bone health in postmenopausal women. Although no definitive conclusions about dosage or formulation can be drawn from this meta-analysis, calcium carbonate at 1,000 mg per day was the most common dosage and is a reasonable choice.

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Cheryl A. Flynn, M.D., M.S., is assistant professor of family medicine at State University of New York Upstate Medical University, Syracuse. She has a special interest in evidence-based medicine.

Address correspondence to Cheryl A. Flynn, M.D., M.S., SUNY Upstate Medical University, 475 Irving Ave., Suite 200, Syracuse, NY 13210 (e-mail: flynnc@upstate.edu). Reprints are not available from the author.

REFERENCES

1. Shea B, Wells G, Cranney A, Zytaruk N, Robinson V, Griffith L, et al. Calcium supplementation on bone loss in postmenopausal women. Cochrane Database Syst Rev 2004:CD004526.

2. Institute for Clinical Systems Improvement. Diagnosis and treatment of osteoporosis. Accessed February 2004 at http://www.icsi.org/knowledge/detail.asp?catID=29&itemID=547.

3. Osteoporosis prevention, diagnosis, and therapy. NIH Consens Statement 2000;17:1-45.

Therapy for Speech and Language Delay

Clinical Question

Which therapies are effective in children with primary speech and language delay?

Evidence-Based Answer

Speech and language therapy is effective in children who have problems with expressive vocabulary and pronunciation. There is insufficient evidence regarding interventions for receptive disorders and mixed results for interventions to improve expressive grammar and sentence structure.

Practice Pointers

Primary speech disorder is defined as a speech and language delay in a child without behavior, hearing, or neurologic impairment. Children with primary speech disorder have a variety of deficits. In adolescence, about one half of children with primary speech disorder have long-term problems with reading and spelling. Speech and language difficulties are common, and there is a range of presentations and etiologies. Some patients have transient, isolated difficulties. Others have more persistent problems with disordered speech and expressive or receptive language.

To evaluate treatments, Law and colleagues searched for randomized, controlled trials on speech and language therapies for children and adolescents with primary speech and language disorders. They found 25 studies of children younger than 15 years that met their selection criteria. Results varied considerably among studies and had wide confidence intervals, but the authors were able to reach some tentative conclusions.

There is some evidence to support speech and language therapy in children with difficulty producing clear speech and expressive vocabulary if difficulties with receptive language are not present. Limited evidence suggests that children with receptive language difficulties may receive less benefit from such therapy. Trained parents and clinicians achieved similar results. Limited data show that group and individual phonology therapy achieved similar results. Interventions lasting more than eight weeks seem to be the most effective. Using peers with normal language as models in intervention is beneficial.

The American Academy of Child and Adolescent Psychiatry1 has published practice parameters for patients with language and learning disorders. For children ages six to 12, the group recommends a clinical diagnostic assessment, including a parent interview, child interview, medical and psychiatric histories, school evaluation, and family history. In the face of limited evidence regarding effective speech and language therapy, these guidelines can help physicians pursue a reasonable diagnostic and treatment plan.

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CLARISSA KRIPKE, M.D.

Law J, et al. Speech and language therapy interventions for children with primary speech and language delay or disorder. Cochrane Database Syst Rev 2003;3:CD004110.

REFERENCES

1. Practice parameters for the assessment and treatment of children and adolescents with language and learning disorders. AACAP. J Am Acad Child Adolesc Psychiatry 1998;37(10 suppl):46S-62S

Neuraminidase Inhibitors for Treatment of Influenza

Clinical Question

How safe, effective, and tolerable are oseltamivir and zanamivir in the treatment of children with influenza?

Evidence-Based Answer

Oseltamivir and zanamivir reduce the duration of illness by up to one day if taken within 36 hours of symptom onset. Oseltamivir (and, probably, zanamivir) also reduces the likelihood of otitis media as a complication of influenza (number needed to treat, approximately 10). There were no data on the medications' efficacy in preventing influenza. Both medications are well tolerated and safe.

Practice Pointers

Two neuraminidase inhibitors, oseltamivir and zanamivir, are approved for use in children. Oseltamivir, which is approved for use in children older then one year, is taken twice daily for five days in dosages of 30 mg (in children weighing less than 15 kg), 45 mg (in children 15 to 22 kg), 60 mg (in children 23 to 40 kg) or 75 mg (in children more than 40 kg). Oseltamivir costs $33 to $67 per treatment course, depending on the dosage. (Prices represent estimated cost to the pharmacist based on average wholesale prices in Red book. Montvale, N.J.: Medical Economics Data, 2004. Cost to the patient will be higher, depending on prescription filling fee.)

Zanamivir, an inhaled agent approved for use in children older than seven years, is taken as two puffs every 12 hours for five days and costs $50 per course. Patients must begin taking oseltamivir or zanamivir within 36 hours of symptom onset.

Matheson and colleagues identified three double-blinded, randomized, placebo-controlled trials of 1,500 children with a clinical diagnosis of influenza (i.e., fever and at least two of the following symptoms: cough, headache, myalgia, sore throat, fatigue). In approximately 53 percent of the children, influenza was eventually confirmed by laboratory tests.

In the 1,500 children with clinically diagnosed influenza, oseltamivir reduced symptoms by a mean of 21 hours, and zanamivir reduced symptoms by a mean of 12 hours. In children with laboratory-confirmed influenza, oseltamivir and zanamivir reduced symptoms by 36 and 30 hours, respectively. In children with asthma and laboratory-confirmed influenza, the duration of illness was reduced by only 10 hours (P = NS).

Oseltamivir reduced the likelihood of acute otitis media from 28 to 17 percent (P = .005) and of bronchitis from 21 to 12 percent (P<.05). Zanamivir use was associated with a nonsignificant reduction in the likelihood of otitis media (23 to 16 percent, P = NS).

Although vomiting was more common in children taking zanamivir (15 percent versus 9 percent in children taking oseltamivir), both drugs were well tolerated, with pooled withdrawal rates similar to those of placebo.

MARK H. EBELL, M.D., M.S.

Matheson NJ, et al. Neuraminidase inhibitors for preventing and treating influenza in children. Cochrane Database Syst Rev 2003;3:CD002744.

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