In vitro anti-resorptive activity and prevention of ovariectomy-induced osteoporosis in female Sprague-Dawley rats by ormeloxifene, a selective estrogen receptor modulator

M. Arshad, S. Sengupta, S. Sharma, R. Ghosh, V. Sawlani, M. M. Singh

Research output: Contribution to journalArticlepeer-review

27 Scopus citations


Antiosteoporotic activity of ormeloxifene, a multifunctional SERM, using inhibition in parathyroid hormone (PTH) induced resorption of 45Ca from prelabeled chick and rat fetal limb bones in chase cultures and modulation of certain biochemical markers of bone turnover and bone mineral density (BMD) in ovariectomized adult female rats, was investigated. Ormeloxifene concentration-dependently inhibited PTH-induced resorption of 45Ca from chick fetal femora with treated/control (T/C) ratio of 0.71, 0.32 and 0.20 at 50, 100 and 200 μM concentration, in comparison to 0.49, 0.53 and 0.95 in case of CDRI-85/287 (a pure antiestrogen), tamoxifen and ethynylestradiol (100 μM), respectively. Using rat fetal limb bones, ormeloxifene (100 μM) exhibited T/C ratio of 0.67, in comparison to 1.43 with PTH alone. Heat-killed bones exhibited negligible resorption (2.9%; T/C: 0.098) in response to PTH. In adult female rats, ormeloxifene (1.25 and 12.5 mg/kg per day) inhibited ovariectomy-induced increase in serum total and bone-specific alkaline phosphatase and osteocalcin and urine calcium/creatinine ratio to almost intact control level. Ovariectomy was accompanied by marked decrease in bone mineral density of isolated femur and tibia, being maximum in femur neck (28.3%; P<0.01) and midshaft (23.7%; P<0.01), but only marginal (6.7%; P>0.05) in region proximal to tibio-fibular separation point. Decrease in BMD based on T-/Z-score, too, was >2.5 S.D. than mean value of normal young adult/age-matched females. This was prevented by ormeloxifene and the effect, though apparently more in females supplemented with higher dose of ormeloxifene, was not always significantly different and clear dose-response was not evident until BMD data was evaluated on T-/Z-score basis. The analysis also demonstrated much higher threshold level of tibia than femur and more so for their mid-shafts. Increase in BMD of isolated bones was also observed in ormeloxifene-treated intact females, without significantly altering biochemical markers of bone turnover or uterine weight. Findings suggest potential of ormeloxifene in management of post-menopausal osteoporosis and beneficial effect on BMD in women taking this SERM for contraception or any hormone-related clinical disorder.

Original languageEnglish (US)
Pages (from-to)67-78
Number of pages12
JournalJournal of Steroid Biochemistry and Molecular Biology
Issue number1-2
StatePublished - Jun 2004
Externally publishedYes

Bibliographical note

Funding Information:
Authors thank Dr. C.M. Gupta, Director for interest in the study, Dr. S. Ray for supply of ormeloxifene, Ms. Mohini Chhabra for technical assistance, Mr. B.R. Verma and Mr. Manoj Dubey for BMD measurements, Dr. Mukesh Srivastava for statistical analysis and Mr. B.P. Mishra and Mr. Jagdish Prasad for handling of animals. This study received financial support from the Ministry of Health and Family Welfare, Government of India. CDRI communication no. 6252.


  • Antiosteoporotic
  • BMD
  • Biochemical markers of bone turnover
  • Ca resorption in vitro
  • Isolated bones
  • Ormeloxifene


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