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Vitamin D Supplementation in Postmenopausal Black Women

Department of Medicine, Winthrop-University Hospital, Mineola, New York 11530

Address all correspondence and requests for reprints to: John F. Aloia, M.D., Winthrop-University Hospital, 259 First Street, Mineola, New York 11501.

	Abstract

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Black women have lower levels of serum 25-hydroxyvitamin D (25OHD) with higher serum PTH levels than white women. Correction of these alterations in the vitamin D-endocrine system could lead to less bone loss in postmenopausal women and, consequently, preservation of bone mass. Ten healthy postmenopausal black women were given 20 µg vitamin D₃ daily for 3 months. At the end of the study, mean serum 25OHD levels had increased from 24 to 63 nmol/L. Serum intact PTH and nephrogenous cAMP declined significantly, and there was a 21% drop in the fasting urinary N-telopeptide of type I collagen. Vitamin D₃ supplementation raises serum 25OHD levels in postmenopausal black women, decreases secondary hyperparathyroidism, and reduces bone turnover. These findings should spur further investigation of the use of vitamin D supplementation in the prevention of osteoporosis in this population.

	Introduction

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STRATEGIES for the prevention of osteoporosis have not been developed extensively in black women because this is a less common disorder than in other ethnic groups. However, black women have about 40% the incidence of osteoporotic fractures as white women; as the longevity of the black population increases, osteoporosis will become increasingly prominent as a health problem (1). As black women have a higher peak musculoskeletal mass, a strategy designed to prevent postmenopausal bone loss would be appropriate (2).

Black women have lower serum 25-hydroxyvitamin D (25OHD) levels as a result of reduced absorption of sunlight by the skin and have higher levels of serum PTH, serum 1,2-dihydroxyvitamin D [1,25-(OH)₂D] and urinary cAMP than whites (3). These findings are consistent with the presence of secondary hyperparathyroidism resulting from suboptimal serum 25OHD levels. An autopsy study provided further evidence for parathyroid hyperplasia in this population (4). Thus, vitamin D supplementation would be expected to reduce serum PTH levels and involutional bone loss.

Correction of secondary hyperparathyroidism with vitamin D supplementation has been shown to be useful in reducing bone loss in the elderly white population (5, 6). Administration of 25OHD corrects the hyperparathyroidism seen in black women (7). The current study was designed to examine 1) whether supplementation with 20 µg vitamin D₃ daily corrects the reduced serum levels of vitamin D and the secondary hyperparathyroidism in postmenopausal black women and 2) whether vitamin D supplementation reduces bone remodeling.

	Experimental Subjects

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All patients were healthy postmenopausal African-American women, aged 60–80 yr. Before entry into the study, all subjects signed a consent form, which was approved by the institutional review board of Winthrop-University Hospital. The subjects had a baseline evaluation and two follow-up evaluations, one at 4 weeks to monitor compliance and the last one at 12 weeks. At the baseline visit, vitamin D₃ was dispensed as tablets of 10 µg vitamin D₃ each, and all subjects were instructed to take two tablets orally daily. They were advised to continue their usual diet and to avoid any vitamin supplements that contained vitamin D. Dietary calcium and vitamin D consumption were assessed by food recall at each visit (8).

	Materials and Methods

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Serum PTH was measured by the Allegro intact-PTH immunoassay purchased from Nichols Institute Diagnostics (San Juan Capistrano, CA) (9). The intraassay coefficient of variation (CV) was 5.2%, and the interassay CV was 9.0%. Serum 1,25-(OH)₂D was measured by radioreceptor binding assay with calf thymus receptor using a kit manufactured by INCSTAR Corp. (Stillwater, MN) (10). The intraassay CV was 8.5%, and the interassay CV was 17.3%. Serum 25OHD was measured by a RRA purchased from Nichols Institute Diagnostics. The intraassay CV was 4.1%, and the interassay CV was 7.0%. Plasma and urinary cAMP were measured by RIA (NEN Life Science Products, North Billerica, MA). Serum calcium was measured by atomic absorption spectrophotometry (model 560, Perkin-Elmer Corp., Norwalk, CT). Serum inorganic phosphate was measured colorimetrically (11). Serum and urinary creatinine were determined by the method of Heinegard and Tiderstsrom (12). Urinary cross-linked N-telopeptide of type I collagen was measured using an enzyme-linked immunoabsorbent assay manufactured by Ostex International, Inc. (Seattle, WA). The intraassay variability was less than 6.4%, and the interassay variability was 7.4%.

Statistical analysis

The biochemical data were analyzed by paired t test, comparing baseline values with values obtained after 12 weeks. The dietary variables were evaluated by repeated measures ANOVA with a Tukey post-hoc analysis. Continuous variables are reported as means, with ranges in parentheses.

	Results

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Clinical characteristics

The mean body mass index was 27.4 kg/m² (24–32 kg/m²). The mean body weight was 69.7 kg (54–88 kg). The mean daily dietary calcium intake was 400 mg/day (150–650 mg/day). Dietary variables did not change significantly at any of the visits. All 10 subjects attended every visit, and compliance (determined by pill count) was 98%.

Laboratory (Fig. 1)

Seven of the subjects had a baseline level of serum 25OHD below 25 nmol/L; all subjects had a baseline level below 50 nmol/L. Baseline levels of serum PTH were above the kit manufacturer’s normal range in 4 of 10 subjects. The serum level of 25OHD increased after supplementation to a level above 50 nmol/L in 9 of 10 subjects. After 12 weeks of using 20 µg vitamin D₃ supplementation, serum intact PTH and nephrogenous cAMP levels had declined significantly compared to the baseline levels. Serum 1,25-(OH)₂D levels declined in 9 of 10 participants [baseline, 112.3 ± 8.2 (±SE) pmol/L) and at 12 weeks was 91.7 ± 9.1 pmol/L (P < 0.02). There were no changes in serum calcium or phosphorus. The fasting urinary N-telopeptide/creatinine ratio and nephrogenous cAMP levels declined by 21% after 12 weeks of vitamin D₃ supplementation.

View larger version (26K): [in this window] [in a new window]   Figure 1. Baseline and 12 week values (mean ± SE), respectively, for serum 25OHD (A; 24.4 ± 3.7 and 63.3 ± 3.5 nmol/L; P < 0.0001), serum PTH (B; 64.4 ± 5.43 and 54.2 ± 6.0 pg/mL; P < 0.0001), nephrogenous cAMP (C; 2.23 ± 0.22 and 1.57 ± 0.19 nmol/100 glomerular filtration rate; P < 0.01), and fasting urine N-telopeptide (D; 43.8 ± 4.9 m/L and 34.6 ± 4.0 nmol/L/mmol/L creatinine).

	Discussion

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Malabanan et al. (13) recently suggested that adults over age 49 yr of age may require sufficient vitamin D to attain serum 25OHD levels above 50 nmol/L to achieve optimum serum PTH levels. In that study, 50,000 IU oral vitamin D were given weekly. The current study suggests that lower doses of vitamin D may be effective in raising serum 25OHD levels. However, serum PTH levels did not decline into the normal range in three of the four subjects with elevated baseline levels. Unless longer term supplementation suppresses these levels, a higher dose of vitamin D₃ may be needed. Indeed, there is convincing evidence that levels of serum 25OHD of at least 75 nmol/L should be attained (14). Seasonal fluctuations in serum PTH are prevented at this level (15, 16, 17). This is also the level above which serum PTH no longer increases (18, 19).

Bone turnover also declined in black women in this study, suggesting that vitamin D supplementation may be a useful strategy for preventing osteoporosis. There are a number of caveats in reaching this conclusion: 1) seasonal changes in sunlight could have influenced vitamin D levels; and 2) the changes in PTH and urinary N-telopeptide could reflect the remodeling transient, so that changes detected at 12 weeks will not be sustained (20). A long term, double blinded, randomized, dose-ranging, placebo-controlled study that includes bone mineral density measurements should be conducted.

Received April 2, 1999.

Revised July 2, 1999.

Accepted July 22, 1999.

	References

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