Effects of transdermal versus oral hormone replacement therapy on bone density in spine and proximal femur in postmenopausal women

Stevenson, J. Court; Cust, MP; Gangar, KF; Hillard, TC; Lees, Belinda; Whitehead, MI

doi:10.1016/0020-7292(91)90649-p

Cited by 41 publications

(56 citation statements)

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“…Clodronate provided an additional benefit for post-menopausal breast cancer patients. In fact, the clodronate-induced increase in bone mass was quite similar to that obtained on oestrogen replacement therapy after a natural menopause (Ettinger et al, 1987(Ettinger et al, , 1992Stevenson et al, 1990).…”

Section: Discussionsupporting

confidence: 73%

Clodronate improves bone mineral density in post-menopausal breast cancer patients treated with adjuvant antioestrogens

Saarto

Blomqvist²,

Välimäki³

et al. 1997

Br J Cancer

115

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Summary The effect of clodronate on bone mineral density (BMD) was studied in 121 post-menopausal breast cancer women without skeletal metastases. In addition, two antioestrogens, tamoxifen and toremifene, were compared in their action on bone mineral density. Patients were randomized to have an adjuvant antioestrogen treatment either 20 mg of tamoxifen or 60 mg of toremifene daily for 3 years. In addition all patients were randomized to have 1600 mg of oral clodronate daily or to act as control subjects. BMD of the lumbar spine and femoral neck were measured by dual-energy radiographic absorptiometry before therapy and at 1 and 2 years. At 2 years, clodronate with antioestrogens markedly increased BMD in the lumbar spine and femoral neck by 2.9% and 3.7% (P = 0.001 and 0.006 respectively). There were no significant changes in BMD in the patients given antioestrogens only. No significant differences were found between tamoxifen and toremifene on bone mineral density. Clodronate with antioestrogens significantly increased bone mass in the lumbar spine and femoral neck. Both antioestrogens, tamoxifen and toremifene, similarly prevented bone loss in the lumbar spine and femoral neck.Keywords: antioestrogens; bone mineral density; bisphosphonate; breast neoplasm; post-menopausal osteoporosis; toremifene Adjuvant antioestrogen treatment with tamoxifen significantly improves the survival of post-menopausal women with primary breast cancer (EBCTCG, 1992). Tamoxifen has oestrogen agonistic effects on bone and therefore prevents bone loss in postmenopausal women (Love et al, 1992;Ward et al, 1993;Kristensen et al, 1994;Powles et al, 1996). Tamoxifen has been shown to prevent bone loss predominantly in the lumbar spine (Love et al, 1992;Kristensen et al, 1994), but in two randomized studies this was also true for the upper femur (Ward et al, 1993;Powles et al, 1996).Toremifene is a close analogue to tamoxifen with demonstrated efficacy in advanced breast cancer (Valavaara et al, 1988). Compared with tamoxifen, toremifene is more oestrogen antagonistic than agonistic in rat (Di Salle et al, 1990). At present, no data are available on the effect of toremifene on bone.Since bisphosphonates prevent post-menopausal bone loss (Chesnut 1984; Reginster et al, 1989;Storm et al, 1990;Watts et al, 1990;Giannini et al, 1993;Harris et al, 1993;Reid et al, 1994;Filipponi et al, 1995;Liberman et al, 1995) and in advanced breast cancer reduced the development of new bone metastases (Elomaa et al, 1983;Martoni et al, 1991;Paterson et al, 1993;Van Holten Verzantvoort et al, 1993), they are attractive candidates for the treatment of patients with early breast cancer. We performed a prospective, open, randomized study to determine the effect of oral clodronate in post-menopausal women with primary breast cancer treated with adjuvant antioestrogens, Received 24 July 1996 Revised 10 October 1996 Accepted 15 October 1996 Correspondence to: Elomaa, Department of Oncology, Helsinki University Central Hospital, Haartmaninkatu 4, FIN-00290 Hels...

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Section: Discussionsupporting

confidence: 73%

Clodronate improves bone mineral density in post-menopausal breast cancer patients treated with adjuvant antioestrogens

Saarto

Blomqvist²,

Välimäki³

et al. 1997

Br J Cancer

115

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“…After menopause, an imbalance between rates of bone formation and bone resorption, favoring the latter, leads to an accelerated bone loss during the first years after menopause (Garnero et al 1996, Clarke & Khosla 2010. This rapid bone loss can be prevented by estrogen administration, and characteristically results in an increase in bone mineral density during the first months of treatment (Lindsay et al 1976, 1980, Stevenson et al 1990. Additionally, the loss of testicular function also underlies bone loss in men.…”

Section: Sex Steroid Hormones Maintain Skeletal Integritymentioning

confidence: 99%

The mutual dependence between bone and gonads

Karsenty¹

2012

Journal of Endocrinology

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It has long been known that sex steroid hormones regulate bone mass accrual. This observation raises the testable hypothesis that bone may in turn regulate the synthesis and secretion of sex steroid hormones in one or both genders. This hypothesis is comprised within a more general hypothesis that bone mass, energy metabolism, and reproduction are regulated coordinately. The identification of osteocalcin as an osteoblast-specific secreted molecule allows us to address this question in molecular terms. This review details how the regulation of male fertility by osteocalcin was unraveled, and how osteocalcin signaling in Leydig cells of the testis occurs. It also discusses the implication of this novel mode of regulation of testosterone synthesis observed in males but not in females.

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“…Although oral and transdermal estrogen have demonstrated their efficacy in preventing postmenopausal bone loss (4,16), both of them have some disadvantages: the significant intestinal and hepatic first pass effects for the oral formulation as outlined above and the large interindividual variation in bioavailability, variable adhesion, and local dermatological reactions of the transdermal route (17)(18)(19).…”

mentioning

confidence: 99%

Effects of Intranasal 17β-Estradiol on Bone Turnover and Serum Insulin-Like Growth Factor I in Postmenopausal Women

Garnero

Tsouderos

Marton

et al. 1999

The Journal of Clinical Endocrinology &Amp; Metabolism

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Estrogen therapy, using either oral or transdermal routes, decreases bone turnover and prevents postmenopausal bone loss. It has been suggested that oral and transdermal 17␤-estradiol (E 2 ) may have different effects on serum insulin-like growth factor I (IGF-I), a potent bone-forming growth factor. In this study we investigated the effects of a new route of administration, the intranasal E 2 spray (S21400), on bone turnover and circulating IGF-I and IGF-binding protein-3 (IGFBP-3). Four hundred and twenty early postmenopausal women (Ͻ5 yr since menopause; mean age, 52 yr) were enrolled in a 3-month, double blind, placebo-controlled study of four doses of intranasal E 2 (100, 200, 300, and 400 g/day), two doses of oral E 2 valerate (1 or 2 mg/day), and placebo. One hundred and twelve women were further treated for 12 months with intranasal E 2 (300 g/day, i.e. the dose that has been shown to be adequate for the majority of postmenopausal women). Markers of bone resorption (urinary type I collagen C telopeptides) and formation [serum osteocalcin, serum type I collagen N-terminal extension propeptide (PINP), and serum bone alkaline phosphatase (BAP)] were measured at baseline, 1 month, 3 months, and 15 months. Serum IGF-I and IGFBP-3 were measured at baseline, 1 month, and 3 months. Urinary type I collagen C telopeptides decreased significantly in all active treatment groups as soon as 1 month (P Ͻ 0.001 vs. placebo) and continued to decrease at 3 months with a dose effect for intranasal E 2 . Serum osteocalcin and PINP did not change at 1 month for oral E 2 (1 and 2 mg), but decreased significantly at 3 months. In contrast, formation markers increased significantly at 1 month for the two highest doses of intranasal E 2 (P Ͻ 0.01 vs. placebo for osteocalcin and BAP) and did not decrease at 3 months. Oral E 2 induced a marked decrease in circulating IGF-I as early as 1 month, which was amplified at 3 months (Ϫ29% and Ϫ32% for 1 and 2 mg, respectively), whereas no significant change from placebo was observed for intranasal E 2 during the 3-month period. Changes in circulating IGF-I correlated significantly (P Ͻ 0.01) with changes in osteocalcin, PINP, and BAP at 3 months. Oral and intranasal E 2 did not induce any significant change from placebo in serum IGFBP-3 at both 1 and 3 months. After 1 yr of treatment with intranasal E 2 (300 g/day), both resorption and formation markers decreased, reaching the levels in premenopausal women, regardless of the type of treatment during the first 3 months.We conclude that E 2 administered by this new nasal route normalizes bone turnover to premenopausal levels. The delayed decrease in bone formation observed with intranasal E 2 compared to oral E 2 may be related to different effects on serum IGF-I levels. (J Clin Endocrinol Metab 84: 2390 -2397, 1999) E STROGEN supplementation, given mainly as conjugated equine extracts or 17␤-estradiol (E 2 ), has been shown to decrease bone turnover, prevent postmenopausal bone loss, and significantly reduce fracture risk in both ea...

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Effects of transdermal versus oral hormone replacement therapy on bone density in spine and proximal femur in postmenopausal women

Cited by 41 publications

References 0 publications

Clodronate improves bone mineral density in post-menopausal breast cancer patients treated with adjuvant antioestrogens

Clodronate improves bone mineral density in post-menopausal breast cancer patients treated with adjuvant antioestrogens

The mutual dependence between bone and gonads

Effects of Intranasal 17β-Estradiol on Bone Turnover and Serum Insulin-Like Growth Factor I in Postmenopausal Women

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