Effect of hormone replacement therapy on bone mineral density in postmenopausal women with mild primary hyperparathyroidism. A randomized, controlled trial.
BACKGROUND
Most patients with primary hyperparathyroidism are postmenopausal women. The presence of osteopenia in persons with mild primary hyperparathyroidism is considered an indication for parathyroidectomy. No prospective, controlled trials have assessed medical therapies for osteopenia in primary hyperparathyroidism.


OBJECTIVE
To examine the effects of estrogen-progestin therapy (hormone replacement therapy) on bone mineral density and biochemical indices in postmenopausal women with mild primary hyperparathyroidism.


METHODS
Double-blind, randomized, placebo-controlled trial.


METHODS
University teaching hospital.


METHODS
42 postmenopausal women with mild primary hyperparathyroidism.


METHODS
Patients were randomly assigned to receive either conjugated estrogens, 0.625 mg/d, and medroxyprogesterone, 5 mg/d, or placebo.


METHODS
Bone mineral densities of the total body, lumbar spine, proximal femur (femoral neck, Ward triangle, trochanter), and proximal forearm were measured every 6 months using dual-energy x-ray absorptiometry. Biochemical indices of bone turnover and calcium metabolism were measured at baseline, 6 months, and 2 years.


RESULTS
In the placebo group, bone mineral densities of the total body and the proximal forearm decreased significantly from baseline (mean +/- SE, -2.3% +/- 0.7% [p = 0.005] and -3.5% +/- 1.2% [p = 0.01], respectively). At the other sites, bone mineral density also tended to decline. In the hormone replacement therapy group, bone mineral density increased from baseline in the total body (1.3% +/- 0.4%; P = 0.004), lumbar spine (5.2% +/- 1.4%; p = 0.002), and femoral neck (3.4% +/- 1.5%; p = 0.05). The between-group differences in bone mineral density at the end of the study ranged from 3.6% to 6.6% and were significant at all sites (P > 0.001 and P < 0.05) except for the Ward triangle (p = 0.06). In the hormone replacement therapy group, serum alkaline phosphatase levels decreased by 22% (p = 0.0004 compared with baseline), urinary hydroxyproline excretion decreased by 42% (p = 0.0004), urinary N-telopeptide excretion decreased by 54% (p = 0.001), and urinary calcium excretion decreased by 45% (p = 0.007). Hormone replacement therapy did not change levels of serum ionized calcium or intact parathyroid hormone.


CONCLUSIONS
Although hormone replacement therapy has little effect on serum calcium levels, it suppresses bone turnover, reduces urinary calcium excretion, and increase bone mineral density throughout the skeleton in postmenopausal women with mild primary hyperparathyroidism. This therapy is thus an important management option for these patients.
Grey
A B
AB
University of Auckland, New Zealand.
Stapleton
J P
JP
Evans
M C
MC
Tatnell
M A
MA
Reid
I R
IR
D000368:Aged; D015519:Bone Density / Q000187:drug effects*; D001851:Bone Diseases, Metabolic / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D002118:Calcium / Q000378:metabolism; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D015914:Estrogen Replacement Therapy; D004966:Estrogens, Conjugated (USP) / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D006961:Hyperparathyroidism / Q000150:complications*; D017258:Medroxyprogesterone Acetate / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D045167:Progesterone Congeners / Q000009:adverse effects / Q000627:therapeutic use
D004966:Estrogens, Conjugated (USP); D045167:Progesterone Congeners; D017258:Medroxyprogesterone Acetate; D002118:Calcium