An open, crossover trial of calcium-fortified milk in prevention of early postmenopausal bone loss.

OBJECTIVE: To establish whether calcium-enriched milk reduces bone loss in women who are within five years of the menopause and have a basal calcium intake < or = 1,250 mg. DESIGN: Two-year open, crossover study. SETTING: A community-based study carried out in Adelaide, South Australia, between September 1997 and June 2000. PARTICIPANTS: 115 women recruited by newspaper advertisement, who were less than five years postmenopausal, were not taking hormone or other therapy that could affect bone and had a usual calcium intake < or = 1,250 mg daily. INTERVENTION: Participants were randomly allocated to Group 1 (who received a supplement of 3 L of calcium-fortified milk weekly in the first year) or Group 2 (who followed their usual diets in the first year). In the second year, Group 1 reverted to their usual diets, and Group 2 received the milk supplement. MAIN OUTCOME MEASURES: Difference in loss of bone mineral density (BMD) at the spine and forearm in the same individuals on and off the milk supplement; urinary excretion of bone resorption markers in a subset of 72 participants in the first year. RESULTS: With each woman serving as her own control, the rate of bone loss from the spine was 1.76 percentage points less when the women were taking the milk supplement than when they were on their usual diet (95% CI, 0.54%-2.98%; P=0.006). However, there was no significant difference in bone loss in the forearm. Fasting urine levels of two markers of bone resorption (hydroxyproline and deoxypyridinoline) were significantly lower in 36 women in the milk group than in 36 women in the usual-diet group (P=0.03 for both markers). CONCLUSION: Supplementing the diet with calcium-fortified milk early in the postmenopausal period delays bone loss at the spine but not at the forearm, and reduces the excretion of bone resorption markers.

The 5-year reproducibility of calcium-related biochemical variables in postmenopausal women.

A total of 19 measured and derived bone-related biochemical variables were determined in 307 postmenopausal volunteers on two occasions, 5 years apart. The plasma variables with the highest coefficients of determination (r2) were plasma globulins, alkaline phosphatase, creatinine and calculated ionized and ultrafiltrable calcium. In the urine, the highest r2 values were in respect of fasting urine calcium excretion corrected for urine sodium, hydroxyproline excretion, and the maximal renal tubular reabsorption of calcium and phosphate (TmCa/GFR and TmP/GFR). The components of variance of TmCa/GFR and TmP/GFR show marked individuality but their methods determination meet the criterion for acceptable analytical goals. We conclude that most of the measured and derived bone-related biochemical variables in fasting plasma and urine are sufficiently reproducible in postmenopausal women to be useful for ranking individuals for a period up to 5 years.

A 5-year longitudinal study of forearm bone mass in 307 postmenopausal women.

We measured forearm bone mineral content at the beginning and end of a 5 year period in 307 untreated postmenopausal volunteers. We also measured height, weight, and a number of biochemical variables in plasma and urine after an overnight fast. The initial mean age of the subjects was 59.0 years (range 39-72), and the mean years since menopause was 10.0 (range 1-37). The mean forearm BMC fell from 1034 +/- 9.6 (SEM) to 982 +/- 9.3 mg/cm (P < 0.001). The coefficient of correlation between the first and second measurements was 0.96. The mean rate of change was -1.0% per annum (with a 99% range of -4 to 1% per annum), which agreed well with previous estimates from cross-sectional data. There was a significant negative correlation between rate of change in bone mass and initial value (r = -0.23; P < 0.001), which was eliminated by expressing change as a percentage of initial bone mass. Of the other variables measured, the one that was most significantly related to the percentage change in bone mass was the urinary hydroxyproline/creatinine ratio (r = -0.35; P < 0.001), which we regard as a marker only. By stepwise regression, the only significant determinants of the rate of change in bone mass were body weight (positive, P < 0.001), years since menopause (positive, P < 0.005), urine calcium (negative, P < 0.01), and serum estrone (positive, P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Fracture rates calculated from fracture histories in normal postmenopausal women.

STUDY OBJECTIVE: The aim was to estimate fracture rates and fracture prevalence from fracture histories in normal postmenopausal women. DESIGN: Apparently healthy postmenopausal women were recruited by advertising in the media. Fracture histories were obtained by personal interview in 1983 and again by interview or questionnaire in 1988. Fracture rates were calculated prospectively and retrospectively. PARTICIPANTS: 492 women (mean age 58.6 years) were selected from over 1000 applicants on the basis that they were suffering from no disease nor taking any therapy which might affect their bones. MEASUREMENTS AND MAIN RESULTS: Retrospective premenopausal and postmenopausal fracture rates were calculated in 1983, prospective rates calculated from 1983 to 1988, and retrospective rates checked again on the second occasion. The retrospective and prospective fracture rates were very similar. The five year fracture rates were low and steady until the menopause, when they rose by a factor of 10 and reached a new plateau after about 15 years. The results were comparable to those obtained from hospital statistics. CONCLUSIONS: The menopausal rise in fracture rates not only involves wrist fractures but most peripheral fractures, and probably reflects postmenopausal loss of trabecular bone. Meaningful fracture rates can be calculated from individual fracture histories in a well defined population. This technique may be particularly useful in developing countries where public health data may be incomplete.

Fracture rates as a function of forearm mineral density in normal postmenopausal women: retrospective and prospective data.

Fracture histories were obtained from 492 normal postmenopausal women in 1983 and again in 1988, and related to forearm mineral content and density determined in 1983. All peripheral fractures, except those attributable to road traffic accidents, were included. There was only one hip fracture in the series. The total number of postmenopausal fractures was 183 in 149 subjects. In both the retrospective and prospective studies, fracture rates were inversely related to bone status and more significantly to bone density than to bone mass. In the pooled data, the fracture rate was three times as high in women with bone densities more than 4 standard deviations below the young normal mean as in those with bone densities above the mean. On logistic regression, the adjusted relative risk of fracture (odds ratio) in subjects more than 4 standard deviations below the young mean compared with those above the mean was 5.5 (2.7-11.4).

Effect of salt restriction on urine hydroxyproline excretion in postmenopausal women.

Fasting calcium and hydroxyproline excretion are related to fasting sodium excretion in postmenopausal women. We postulate that calcium excretion is sodium dependent and that hydroxyproline excretion is calcium dependent. Therefore, we sought to lower urinary hydroxyproline, which is a marker of bone resorption, by lowering urinary sodium. Fasting urine samples were obtained from 59 postmenopausal women before and after 2 to 7 days of dietary salt restriction. The urinary sodium-to-creatinine ratio fell from 16 to 7; calcium to creatinine, 0.30 to 0.26; and hydroxyproline to creatinine, 18.2 to 16.8. In the 28 subjects with starting sodium-to-creatinine ratios greater than 15, the hydroxyproline-to-creatinine ratio fell from 19.6 to 16.3. Salt restriction may be one way of reducing bone resorption in postmenopausal women, particularly in those whose sodium intake is high.