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In vitro anti-resorptive activity and prevention of ovariectomy-induced osteoporosis in female Sprague-Dawley rats by ormeloxifene, a selective estrogen receptor modulator.
J Steroid Biochem Mol Biol. 2004 Jun; 91(1-2):67-78.JS

Abstract

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 microM concentration, in comparison to 0.49, 0.53 and 0.95 in case of CDRI-85/287 (a pure antiestrogen), tamoxifen and ethynylestradiol (100 microM), respectively. Using rat fetal limb bones, ormeloxifene (100 microM) 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.

Authors+Show Affiliations

Division of Endocrinology, Central Drug Research Institute, Lucknow, India.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15261309

Citation

Arshad, M, et al. "In Vitro Anti-resorptive Activity and Prevention of Ovariectomy-induced Osteoporosis in Female Sprague-Dawley Rats By Ormeloxifene, a Selective Estrogen Receptor Modulator." The Journal of Steroid Biochemistry and Molecular Biology, vol. 91, no. 1-2, 2004, pp. 67-78.
Arshad M, Sengupta S, Sharma S, et al. In vitro anti-resorptive activity and prevention of ovariectomy-induced osteoporosis in female Sprague-Dawley rats by ormeloxifene, a selective estrogen receptor modulator. J Steroid Biochem Mol Biol. 2004;91(1-2):67-78.
Arshad, M., Sengupta, S., Sharma, S., Ghosh, R., Sawlani, V., & Singh, M. M. (2004). In vitro anti-resorptive activity and prevention of ovariectomy-induced osteoporosis in female Sprague-Dawley rats by ormeloxifene, a selective estrogen receptor modulator. The Journal of Steroid Biochemistry and Molecular Biology, 91(1-2), 67-78.
Arshad M, et al. In Vitro Anti-resorptive Activity and Prevention of Ovariectomy-induced Osteoporosis in Female Sprague-Dawley Rats By Ormeloxifene, a Selective Estrogen Receptor Modulator. J Steroid Biochem Mol Biol. 2004;91(1-2):67-78. PubMed PMID: 15261309.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - In vitro anti-resorptive activity and prevention of ovariectomy-induced osteoporosis in female Sprague-Dawley rats by ormeloxifene, a selective estrogen receptor modulator. AU - Arshad,M, AU - Sengupta,S, AU - Sharma,S, AU - Ghosh,R, AU - Sawlani,V, AU - Singh,M M, PY - 2002/10/01/received PY - 2004/02/20/accepted PY - 2004/7/21/pubmed PY - 2004/9/15/medline PY - 2004/7/21/entrez SP - 67 EP - 78 JF - The Journal of steroid biochemistry and molecular biology JO - J Steroid Biochem Mol Biol VL - 91 IS - 1-2 N2 - 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 microM concentration, in comparison to 0.49, 0.53 and 0.95 in case of CDRI-85/287 (a pure antiestrogen), tamoxifen and ethynylestradiol (100 microM), respectively. Using rat fetal limb bones, ormeloxifene (100 microM) 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. SN - 0960-0760 UR - https://www.unboundmedicine.com/medline/citation/15261309/In_vitro_anti_resorptive_activity_and_prevention_of_ovariectomy_induced_osteoporosis_in_female_Sprague_Dawley_rats_by_ormeloxifene_a_selective_estrogen_receptor_modulator_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0960076004002262 DB - PRIME DP - Unbound Medicine ER -