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Biochemical bone markers and bone mineral density during postmenopausal hormone replacement therapy with and without vitamin D3: a prospective, controlled, randomized study.
J Clin Endocrinol Metab. 1997 Aug; 82(8):2476-82.JC

Abstract

The effects of postmenopausal hormone replacement therapy (HRT) and vitamin D on the serum concentrations of three bone biochemical markers and their associations with bone mineral density (BMD) were studied in a population-based 1-yr follow-up study. A total of 72 healthy postmenopausal women were randomized into 4 treatment groups: HRT group (sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate), D group (vitamin D3, 300 IU/day), HRT+D group (both of the above), and placebo group (calcium lactate, 500 mg/day). Serum concentrations of osteocalcin (OC) and bone-specific alkaline phosphatase (BAP) were measured as biochemical markers of bone formation, and serum type I collagen carboxy-terminal telopeptide was measured as a marker of bone resorption at baseline and after 6 and 12 months of treatment. To investigate the associations of these markers with BMD, lumbar (L2-L4) and femoral neck BMDs were determined by dual x-ray absorptiometry at baseline and after 2.5 yr of treatment. In both hormone groups, the serum concentrations of the three bone metabolic markers had decreased after 12 months. Those of OC decreased by 29.2% (P = 0.017) in the HRT group and by 37.3% (P = 0.004) in the HRT+D group, and BAP concentrations decreased by 34.4% (P < 0.001) in the HRT group and by 36.2% (P < 0.001) in the HRT+D group. Serum type I collagen carboxy-terminal telopeptide concentrations had decreased by 21.6% (P = 0.012) in HRT group and by 14.1% (P = 0.011) in the HRT+D group. In the D group, the serum concentrations of BAP had decreased by 11.7% (P = 0.040) after 12 months, but the other two markers showed no change. The only change seen in the placebo group was a 19.2% increase in OC concentrations (P = 0.041) after 6 months, but at 12 months, the mean OC level was similar to that at baseline. After 2.5 yr, both lumbar and femoral BMD had decreased in the D group [2.1% (P = 0.022) and 3.6% (P = 0.019), respectively] and in the placebo group [3.3% (P = 0.009) and 2.7% (P = 0.010), respectively], whereas no significant changes occurred in the hormone groups. There were significant inverse correlations between the changes in lumbar and femoral BMDs and changes in all three biochemical markers (r = -0.240 through -0.336; P = 0.005-0.064). Our results suggest that HRT counteracts the biochemical changes caused by increased bone turnover associated with menopause. Importantly, the changes in bone markers correlate with long term changes in BMDs of lumbar spine and femoral neck. Low dose vitamin D treatment, however, seems to have only marginal effects on bone metabolism in early postmenopausal healthy women.

Authors+Show Affiliations

Department of Obstetrics and Gynecology, University Hospital of Kuopio, Finland. anna-mari.heikkinen@pp.inet.fiNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9253321

Citation

Heikkinen, A M., et al. "Biochemical Bone Markers and Bone Mineral Density During Postmenopausal Hormone Replacement Therapy With and Without Vitamin D3: a Prospective, Controlled, Randomized Study." The Journal of Clinical Endocrinology and Metabolism, vol. 82, no. 8, 1997, pp. 2476-82.
Heikkinen AM, Parviainen M, Niskanen L, et al. Biochemical bone markers and bone mineral density during postmenopausal hormone replacement therapy with and without vitamin D3: a prospective, controlled, randomized study. J Clin Endocrinol Metab. 1997;82(8):2476-82.
Heikkinen, A. M., Parviainen, M., Niskanen, L., Komulainen, M., Tuppurainen, M. T., Kröger, H., & Saarikoski, S. (1997). Biochemical bone markers and bone mineral density during postmenopausal hormone replacement therapy with and without vitamin D3: a prospective, controlled, randomized study. The Journal of Clinical Endocrinology and Metabolism, 82(8), 2476-82.
Heikkinen AM, et al. Biochemical Bone Markers and Bone Mineral Density During Postmenopausal Hormone Replacement Therapy With and Without Vitamin D3: a Prospective, Controlled, Randomized Study. J Clin Endocrinol Metab. 1997;82(8):2476-82. PubMed PMID: 9253321.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Biochemical bone markers and bone mineral density during postmenopausal hormone replacement therapy with and without vitamin D3: a prospective, controlled, randomized study. AU - Heikkinen,A M, AU - Parviainen,M, AU - Niskanen,L, AU - Komulainen,M, AU - Tuppurainen,M T, AU - Kröger,H, AU - Saarikoski,S, PY - 1997/8/1/pubmed PY - 1997/8/1/medline PY - 1997/8/1/entrez SP - 2476 EP - 82 JF - The Journal of clinical endocrinology and metabolism JO - J. Clin. Endocrinol. Metab. VL - 82 IS - 8 N2 - The effects of postmenopausal hormone replacement therapy (HRT) and vitamin D on the serum concentrations of three bone biochemical markers and their associations with bone mineral density (BMD) were studied in a population-based 1-yr follow-up study. A total of 72 healthy postmenopausal women were randomized into 4 treatment groups: HRT group (sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate), D group (vitamin D3, 300 IU/day), HRT+D group (both of the above), and placebo group (calcium lactate, 500 mg/day). Serum concentrations of osteocalcin (OC) and bone-specific alkaline phosphatase (BAP) were measured as biochemical markers of bone formation, and serum type I collagen carboxy-terminal telopeptide was measured as a marker of bone resorption at baseline and after 6 and 12 months of treatment. To investigate the associations of these markers with BMD, lumbar (L2-L4) and femoral neck BMDs were determined by dual x-ray absorptiometry at baseline and after 2.5 yr of treatment. In both hormone groups, the serum concentrations of the three bone metabolic markers had decreased after 12 months. Those of OC decreased by 29.2% (P = 0.017) in the HRT group and by 37.3% (P = 0.004) in the HRT+D group, and BAP concentrations decreased by 34.4% (P < 0.001) in the HRT group and by 36.2% (P < 0.001) in the HRT+D group. Serum type I collagen carboxy-terminal telopeptide concentrations had decreased by 21.6% (P = 0.012) in HRT group and by 14.1% (P = 0.011) in the HRT+D group. In the D group, the serum concentrations of BAP had decreased by 11.7% (P = 0.040) after 12 months, but the other two markers showed no change. The only change seen in the placebo group was a 19.2% increase in OC concentrations (P = 0.041) after 6 months, but at 12 months, the mean OC level was similar to that at baseline. After 2.5 yr, both lumbar and femoral BMD had decreased in the D group [2.1% (P = 0.022) and 3.6% (P = 0.019), respectively] and in the placebo group [3.3% (P = 0.009) and 2.7% (P = 0.010), respectively], whereas no significant changes occurred in the hormone groups. There were significant inverse correlations between the changes in lumbar and femoral BMDs and changes in all three biochemical markers (r = -0.240 through -0.336; P = 0.005-0.064). Our results suggest that HRT counteracts the biochemical changes caused by increased bone turnover associated with menopause. Importantly, the changes in bone markers correlate with long term changes in BMDs of lumbar spine and femoral neck. Low dose vitamin D treatment, however, seems to have only marginal effects on bone metabolism in early postmenopausal healthy women. SN - 0021-972X UR - https://www.unboundmedicine.com/medline/citation/9253321/Biochemical_bone_markers_and_bone_mineral_density_during_postmenopausal_hormone_replacement_therapy_with_and_without_vitamin_D3:_a_prospective_controlled_randomized_study_ L2 - https://academic.oup.com/jcem/article-lookup/doi/10.1210/jcem.82.8.4177 DB - PRIME DP - Unbound Medicine ER -