Exercise, Calcium Supplementation May Improve BMD in Postmenopausal Women

News Author: Laurie Barclay, MD

From Medscape Medical News.

Dec. 28, 2005 — Exercise and calcium supplementation improve bone mineral density (BMD) in postmenopausal women, according to the results of a 4-year study reported in the December issue of Osteoporosis International.
"The good news is these long-term data confirmed the potent combination of improved nutrition and increased physical activity to prevent bone loss," principal investigator Timothy Lohman, PhD, from the University of Arizona in Tucson, said in a news release. "The extended use of calcium supplementation and exercise counteracted the typical loss of BMD in women at this age, in a regimen that women really can stick with. This is quite significant for younger women as well, as these exercises and calcium supplementation can help build peak BMD which may prevent health problems and osteoporosis in the future."
In the Bone, Estrogen, Strength Training (BEST) study, 167 postmenopausal, calcium-supplemented (800 mg/day) sedentary women were randomized to a progressive strength training exercise program or to a control group and were followed up for 4 years. Mean age was 56.1 ± 4.5 years, and 54% of the women were using hormone therapy (HT) at baseline. At 1 year, women in the control group were permitted to crossover to the exercise program. The final sample consisted of 23 controls, 55 crossovers, and 89 randomized exercisers.
The prescribed exercise program was 2 sets of 6 to 8 repetitions of exercises at 70% to 80% of 1 repetition maximum, 3 times weekly.
"What sets this regimen apart is the six specific exercises that help build bone in the wrist, hip and spine — three key fracture sites," says BEST Study coinvestigator Lauve Metcalfe, MS, also from the University of Arizona in Tucson. "This type of weight-bearing exercise now is proven to be beneficial and represents a shift in prior bone health recommendations. It previously was thought that any type of exercise was helpful, but now we understand that resistance and weight-bearing exercise are essential."
Dual-energy x-ray absorptiometry (DEXA) was used to measure BMD at baseline and annually thereafter. Average 4-year percentage exercise frequency (ExFreq) was 26.8% ± 20.1% for crossovers (including the first year at 0%) and 50.4% ± 26.7% for exercisers. Average 4-year total confidence interval (CI) was 1,635 ± 367 mg/day, and supplemental calcium intake was 711 ± 174 mg/day.
Adjusted multiple linear regression models revealed that ExFreq was positively and significantly related to changes in femur trochanter (FT) and neck (FN), lumbar spine (LS), and total body (TB) BMD. For women receiving HT, FT BMD increased 1.5%, and the FN and LS BMD increased 1.2% (P < .01) for each SD of percentage ExFreq (29.5% or 0.9 days per week). Women not using HT gained 1.9% and 2.3% BMD at FT and FN, respectively, for every SD of CI (P < .05).
"The significant, positive, association between BMD change and ExFreq supports the long-term usefulness of strength training exercise for the prevention of osteoporosis in postmenopausal women, especially HT users," the authors write. "The positive relationship of CI to change in BMD among postmenopausal women not using HT has clinical implications in light of recent evidence of an increased health risk associated with HT."
Study limitations include allowing controls to cross over to the exercise group of the study after the first year of intervention; potential training time discrepancies between exercisers and crossovers; questionable accuracy of self-reports of exercise; and dropout rates.
"This study supports the long-term benefits of strength training exercise and calcium intake for the prevention of osteoporosis in postmenopausal women," the authors conclude. "Combined with exercise, women may choose to continue HT or increase total calcium intake to around 1,700 mg/day to help prevent osteoporosis."
The National Institute for Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health funded the BEST Study. Mission Pharmacal Co supplied calcium citrate (Citracal) for the study.
Osteoporos Int. 2005;16:2129-2141

FDA OKs Bristol-Myers Drug for Rheumatoid Arthritis

LOS ANGELES (Reuters) Dec 27 - Bristol-Myers Squibb Co. said on Friday that it has won U.S. approval to sell a new type of drug for treating rheumatoid arthritis.

The drug, Orencia (abatacept), is the first approved T-cell co-stimulation modulator. It is administered by monthly intravenous infusion.

Orencia was approved for treating moderate to severe cases of rheumatoid arthritis that do not respond to one or more other therapies.

Three Bristol-Myers studies showed more patients had a 20% improvement in rheumatoid arthritis symptoms when treated with Orencia rather than a placebo. In one study, 61% of Orencia patients, compared with 35% of placebo patients, saw that level of benefit during 6 months of therapy.

Like TNF-alpha inhibitors, Orencia was associated with a risk of infections. Serious infections occurred in 3% of patients treated with Orencia, compared with 1.9% who received a placebo.

Topical Diclofenac Reduces Pain of Knee Osteoarthritis

From Medscape Medical News.

NEW YORK (Reuters Health) Dec 22 - Topical diclofenac gel applied four times daily relieves symptoms of osteoarthritis (OA) of knee, results of a German study demonstrate.

Oral nonsteroidal anti-inflammatory drugs (NSAIDs) have considerable gastrointestinal toxicity, Dr. Fritz U. Niethard and colleagues note in the Journal of Rheumatology for December, whereas systemic exposure from topical NSAIDs is estimated at 10% of that following oral administration.

Dr. Niethard, from Universitatsklinikum Aachen and his team enrolled patients with unilateral OA of the knee, with radiographic signs, pain scores of at least 50 mm on a 100-mm visual analog scale and at least "moderate" pain on a 4-point scale.

After a washout phase in which they discontinued analgesic medication, patients were randomly assigned to topical diclofenac diethylamine gel 1.16% (Voltaren Emulgel, Novartis) or placebo to be rubbed into the knee 4 times daily for 3 weeks. The intent-to-treat analysis included 117 in the diclofenac arm and 119 in the placebo arm. Patients were permitted up to four tablets per day of acetaminophen 500 mg as rescue medication.

"Efficacy developed over the course of the first week, reached a peak during the second week, and was maintained over the third week," the authors observe in their report.

According to diaries that the patients kept, diclofenac was significantly superior to placebo gel in pain-on-movement averaged over days 8-21 (average difference 6 mm on the visual analog scale, p = 0.005). During the same period, diclofenac was associated with a lower rating of spontaneous pain (p = 0.02).

Those on active treatment were also more likely than those on placebo treatment to rate the effectiveness of the gel as good, very good, or excellent (69% versus 58%). At week 3, pain score on the Western Ontario and McMaster (WOMAC) Osteoarthritis Index Questionnaire had improved by 47% and 29%, respectively.

Adverse events and results of hematology, serum chemistry and urinary laboratory measures were identical in the two groups. The use of rescue medication was similar in the two groups.

"Diclofenac gel ... should be considered as an appropriate first-line option for the treatment of pain in OA of small and large joints," Dr. Niethard and his associates maintain.

This study was supported by Novartis Consumer Health.

J Rheumatol 2005;32:2384-2392.

Glucocorticoid Injection Appears Helpful in Rheumatoid Arthritis

From Medscape Medical news

By David Douglas

NEW YORK (Reuters Health) Dec 08 - Intra-articular glucocorticoid injections appear to protect cartilage in patients with rheumatoid arthritis (RA), Swedish researchers report in the December issue of Annals of the Rheumatic Diseases. In addition, subsequent bed rest seems to improve results.

Dr. Tomas Weitoft of Gavle Hospital and colleagues note that such treatment is routinely given to RA patients with synovitis. However, there is some concern that this may lead to cartilage breakdown. Another unresolved question is whether joint immobilization leads to better treatment outcome.

To investigate, the researchers studied 20 patients with RA and knee synovitis. They were randomized to treatment with a single glucocorticoid injection followed by 24 hours of bed rest or of normal activity.

Levels of cartilage oligomeric matrix protein (COMP) -- a marker of cartilage turnover -- decreased in both groups, but significantly more so in the resting patients. Serum osteocalcin levels decreased significantly and similarly in both groups, indicating a reduction in bone formation.

In light of these findings, the researchers conclude that the treatment apparently reduces cartilage breakdown. Moreover, they add that the greater drop in serum COMP seen in the resting group may reflect lower clearance from the joint cavity.

If needed, such injections may be given more frequently than the recommended every three months, because they "may be chondroprotective and the suppression of the hypothalamic- pituitary-adrenal is short-termed and reversible," Dr. Weitoft told Reuters Health.

However, he added, "a need for very frequent injections may indicate an uncontrolled disease and other changes of medication should be considered."

Ann Rheum Dis 2005;64:1750 -1753.

TNF inhibitors, MTX reduce RA cardiovascular deaths

Nov 25, 2005 Janis Kelly

San Diego, CA - TNF inhibitors and methotrexate (MTX) decrease the risk of death, especially cardiovascular (CV) death, in rheumatoid-arthritis (RA) patients, whereas prednisone increases mortality, Kaleb Michaud (Stanford University, CA) reported at the 2005 ACR/ARHP Annual Scientific Meeting [1].

According to Michaud, anti-TNF use was associated with a reduced risk of mortality (hazard ratio [HR] 0.69), as was MTX (HR 0.84). Prednisone use, however, was associated with increased mortality (HR 1.63). "Despite more severe RA at onset, anti-TNF and MTX therapies appear to convey a mortality benefit," said Michaud.

First study to show survival benefit
Michaud and coauthor Dr Frederick Wolfe (National Data Bank for Rheumatic Diseases, Wichita, KS) analyzed data from a long-term outcome study of 19 580 patients with RA. During 63 811 patient-years of follow-up, there were 1129 deaths. The researchers used initial Health Assessment Questionnaire (HAQ) scores to adjust for baseline severity, time-varying HAQ scores to account for changes in severity as the result of therapy, and a baseline comorbidity index of 13 medical conditions to adjust for baseline concomitant diseases.

"In clinical trials, anti-TNF therapy is superior to conventional therapies for the treatment of rheumatoid arthritis. However, there is, as yet, no evidence of long-term benefit for this treatment, and there is concern regarding long-term toxicity. Studies of mortality can provide a 'hard' end point that can provide evidence regarding these issues. Such studies usually require many years of follow-up, unless a very large sample is available. We used such a sample to assess the effect of contemporary treatment on mortality in RA," Michaud said.

The analysis showed that 45% of deaths were due to cardiovascular disorders, 29% to lung disorders, 23% to malignancies, and 8% to infections. Prednisone was associated with increased mortality (HR 1.63). TNF inhibitors were associated with reduced mortality (HR 0.69), as was MTX (HR 0.84).

Given the importance of CV risk in this population, the effect of treatment on risk of CV death was particularly interesting. Michaud reported that MTX, infliximab, and etanercept were all strongly associated with a decreased risk of CV mortality (HR 0.61-0.74), whereas prednisone was associated with an increased risk of CV mortality.

This raises the intriguing question of whether the improvement in CV risk observed in patients taking TNF inhibitors or MTX was due to treatment or reflected a lowering of CV risk attributable to less use of prednisone.

"It is well documented that rheumatoid-arthritis patients have [higher mortality rates than] the general population. Although these patients and their physicians should continue to monitor and make sound and personalized decisions about their prescribed therapies, . . . they should note that the use of methotrexate and anti-TNF therapy improves survival," Michaud concluded.

Source

Michaud K, Wolfe F. Reduced mortality among RA patients treated with anti-TNF therapy and methotrexate. 2005 ACR/ARHP Annual Scientific Meeting; November 12-17; San Diego, CA. Poster 296.