EFFECTS OF NORETHISTERONE ON BONE-RELATED BIOCHEMICAL VARIABLES AND FOREARM BONE-MINERAL IN POSTMENOPAUSAL OSTEOPOROSIS

OBJECTIVE Progestogens may be a useful therapeutic alternative to oest rogen in the treatment of post-menepausal osteoporosis. The purpose of this study was to determine the effects of norethisterone on forearm bone mineral content and bone related biochemical variables in patient s with post-menopausal osteoporosis. DESIGN/PATIENTS The effects of tr eatment with norethisterone (5 mg/day) on bone related biochemical var iables was determined in 44 women with post-menopausal osteoporosis. T he effects of norethisterone on forearm bone mineral content (FMC) wer e evaluated by serial measurements in 39 of these women. MEASUREMENTS We measured forearm mineral content, forearm mineral density, forearm fat content and fat-corrected forearm mineral density. Biochemical mea surements included plasma calcium and plasma calcium fractions (ionize d, protein bound, complexed and ultrafiltrable), alkaline phosphatase, bicarbonate, phosphate, albumin and globulins, serum parathyroid horm one, osteocalcin and 1,25-dihydroxyvitamin D, radiocalcium (Ca-45) abs orption and fasting urinary calcium/creatinine, sodium/creatinine, pho sphate/creatinine and hydroxyproline/creatinine molar ratios. RESULTS After 4 months of treatment norethisterone produced a fall in plasma c alcium (mean +/- SEM from 2.40 +/- 0.14 to 2.32 +/- 0.13 mmol/l, P < 0 .001), primarily in the non-ionized calcium, due to a decrease in plas ma bicarbonate (from 29 +/- 0.28 to 27 +/- 0.28 mmol/l, P < 0.001). Th ere were decreases in urinary calcium/creatinine (from 0.41 +/- 0.03 t o 0.19 +/- 0.02, P < 0.01) and sodium/creatinine (from 15 +/- 1 1 to 1 0 +/- 0 93, P< 0.001) molar ratios and a rise in the renal tubular max imum for calcium reabsorption (TmCa) (from 2.36 +/- 0.041 to 2.55 +/- 0.059 mmol/l of glomerular filtrate, P < O.001). Plasma phosphate, uri nary phosphate/creatinine and tubular maximum for phosphate reabsorpti on (TMP) all fell (P < O.01). Both the urinary hydroxyproline/creatini ne (P < 0.001) and plasma alkaline phosphatase (P < 0.001) fell. Serum parathyroid hormone rose from 4.1 +/- 0.36 to 5.5 +/- 0.51 pmol/l (P < 0.02) and radiocalcium absorption increased from 0.67 +/- 0.08 to 0. 81 +/- 0.10 fx/h (P < 0.01). There was no change in serum 1,25-dihydro xy vitamin D. After treatment with norethisterone for 4 months there w as an increase in forearm bone mineral content (P < 0.05) and a decrea se in forearm fat content (P < 0.02). After two years treatment with n orethisterone fat-corrected forearm bone mineral content rose (mean ch ange 17.0 +/- 5.5 mg/cm, P < 0.01). CONCLUSIONS These results suggest that norethisterone prevents bone loss in post-menopausal osteoporosis by decreasing bone turnover, has a vitamin-D independent effect on in testinal calcium absorption, and increases serum parathyroid hormone l evels.