BIOCHEMICAL BONE MARKERS AND BONE-MINERAL DENSITY DURING POSTMENOPAUSAL HORMONE REPLACEMENT THERAPY WITH AND WITHOUT VITAMIN-D-3 - A PROSPECTIVE, CONTROLLED, RANDOMIZED STUDY
Am. Heikkinen et al., BIOCHEMICAL BONE MARKERS AND BONE-MINERAL DENSITY DURING POSTMENOPAUSAL HORMONE REPLACEMENT THERAPY WITH AND WITHOUT VITAMIN-D-3 - A PROSPECTIVE, CONTROLLED, RANDOMIZED STUDY, The Journal of clinical endocrinology and metabolism, 82(8), 1997, pp. 2476-2482
The effects of postmenopausal hormone replacement therapy (KRT) and vi
tamin 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 postme
nopausal women were randomized into 4 treatment groups: HRT group (seq
uential combination of 2 mg estradiol valerate and 1 mg cyproterone ac
etate), D group (vitamin D-3, 300 IU/day), HRT+D group (both of the ab
ove), and placebo group (calcium lactate, 500 mg/day). Serum concentra
tions 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 b
one resorption at baseline and after 6 and 12 months of treatment. To
investigate the associations of these markets with BMD, lumbar (L2-L3)
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 s
erum 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 concentrat
ions 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 tel
opeptide concentrations had decreased by 21.6% (P = 0.012) in HRT grou
p and by 14.1% (P = 0.011) in the HRT+D group. In the D group, the ser
um concentrations of BAP had decreased by 11.7% (P = 0.040) after 12 m
onths, but the other two markers showed no change. The only change see
n 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 simila
r to that at baseline. After 2.5 yr, both lumbar and femoral BMD had d
ecreased in the D group [2.1% (P = 0.022) and 3.6% (P = 0.019, respect
ively] and in the placebo group [3.3% (P = 0.009) and 2.7% (P = 0.010)
, respectively], whereas no significant changes occurred in the hormon
e groups. There were significant inverse correlations between the chan
ges in lumbar and femoral BMDs and changes in all three biochemical ma
rkers (r = -0.240 through -0.336; P = 0.005-0.064). Our results sugges
t that HRT counteracts the biochemical changes caused by increased bon
e 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 onl
y marginal effects on bone metabolism in early postmenopausal healthy
women.