Tibolone & bone

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1446564 & dopt=Abstract

Osteoporos Int 2001;12(6):478-483 Related Articles, Books, LinkOut

Effects of 8 years of treatment with tibolone 2.5 mg daily on postmenopausal

bone loss.

Rymer J, J, Fogelman I.

Department of Obstetrics and Gynaecology, Guy's, King's and St ' Medical

School, London, UK.

janice.rymer@...

The objective of this study was to assess the long-term effects of tibolone 2.5

mg daily (Livial; Organon) on bone

mineral density in recently postmenopausal women. An 8-year, open,

nonrandomized, prospective study was designed to

compare the effects of tibolone 2.5 mg daily (n = 59) with an untreated control

group (n = 51). The subjects of this

study were 110 recently postmenopausal women (6-36 months since last menstrual

period). The main outcome measures were

bone mineral density of the spine and femur, measured by dual-energy X-ray

absorptiometry, and assessment of biochemical

markers of bone metabolism. After 8 years of tibolone use, the mean (+/- SEM)

increase in bone mineral density compared

with baseline was 4.1% +/- 0.8% (p<0.0001) in the spine and 4.6% +/- 1.8% (p =

0.015) in the femoral neck. Over the same

period, bone mineral density in the control group decreased in the spine by

-7.5% +/- 1.1%, (p<0.0001) and in the femur

by -6.7% +/- 1.2% (p<0.0001). The bone resorption marker, calcium/creatinine

ratio, decreased in the tibolone group but

not in the control group. Serum bone formation markers decreased (alkaline

phosphatase) or stayed approximately the same

(osteocalcin) in the tibolone group. Adherence was high, with 58% (34 of 59) of

the tibolone group continuing treatment

for 8 years. We conclude that tibolone 2.5 mg daily prevents bone loss in the

lumbar spine and femoral neck over 8 years

and adherence to treatment is high. The greater bone density compared with

untreated women would be expected to reduce

the risk of bone fractures.

PMID: 11446564 [PubMed - indexed for MEDLINE]

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1428176 & dopt=Abstract

Climacteric 2001 Jun;4(2):120-136 Related Articles, Books, LinkOut

Tibolone and its effects on bone: a review.

Berning B, Bennink HJ, Fauser BC.

Department of Obstetrics and Gynecology, Leyenburg Hospital, The Hague.

This review examines the evidence for the effects of tibolone on bone. Tibolone

is a synthetic steroid with a mixed

(estrogenic-progestogenic-androgenic) hormonal profile. Data suggest a complex

receptor-mediated as well as metabolic

regulation of the activity of tibolone at target tissue level. It has been shown

that tibolone can prevent axial and

appendicular bone loss induced by ovariectomy and/or a low calcium diet in young

and mature rats. In addition, tibolone

increases trabecular and cortical bone mineral density in rats with established

osteopenia. In the rat, treatment with

tibolone results in an increased strength of the femoral neck and of the

vertebral body, similar to that found with

estrogens. The protective effect on bone can be blocked by antiestrogens,

indicating that the effect is estrogen

receptor-mediated.

Clinical trials have shown that loss of bone in the spine and proximal hip can

be prevented with tibolone 2.5 mg/day in

early- and late-postmenopausal women.

In addition, a dose of 1.25 mg/day seems also to be effective, especially in

late-postmenopausal women. In women with

established osteoporosis, bone density of the axial and appendicular skeleton

increases with tibolone. In comparative

studies, tibolone 2.5 mg/day seems to be as effective as conventional hormone

replacement therapy regimens. There are no

direct comparative studies between tibolone and bisphosphonates or raloxifene.

Furthermore, to establish the efficacy of

tibolone for prevention of osteoporotic fractures, studies of the magnitude of

reduction in fracture risk remain to be

conducted. Finally, tibolone seems to be effective in preserving bone density in

patients treated with

gonadotropin-releasing hormone agonist.

PMID: 11428176 [PubMed - in process]

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http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve & db=PubMed & list_uids=1\

1384882 & dopt=Abstract

J Steroid Biochem Mol Biol 2001 Jan;76(1-5):231-238 Related Articles, Books,

LinkOut

Tibolone: a steroid with a tissue-specific mode of action.

Kloosterboer HJ.

NV Organon, Research and Development Laboratories, P.O. Box 20, 5340, Oss, The

Netherlands.

h.kloosterboer@...

In postmenopausal women tibolone has proved to prevent bone-loss and relieve

climacteric symptoms as effectively as

estrogens, but it does not stimulate the endometrium and the breast. This

clinical profile strongly suggests that

tibolone is a compound with tissue-specific action. Tibolone is quickly

metabolized into its main active metabolites,

3alpha and 3beta-OH, which are also present in an inactive, sulphated, form. In

addition a Delta4-metabolite is found in

circulation. The 3-OH-metabolites bind only to the estrogen receptor while the

Delta4-isomer shows affinity only to the

progesterone and androgen receptors. Tibolone prevents bone loss in a similar

way to estrogens. Studies on bone mass

using anti-estrogen, antiprogestin and anti-androgen in combination with

tibolone, confirmed the sole involvement of the

estradiol receptor. Increases in skin temperature as well as vaginal atrophy can

be prevented by tibolone in a similar

way to estrogens.

Breast safety studies showed that tibolone clearly inhibited the growth of

tumors in a DMBA model. In breast cell lines,

tibolone profoundly inhibited sulphatase activity and an increase in apoptosis

and decrease in cell proliferation was

found.

The stimulation of the endometrium is prevented by the local formation of the

Delta4-isomer from tibolone or the

3beta-OH-metabolite.

We conclude that tibolone acts as a tissue-specific compound by mediating its

effects via steroid receptors and

enzymatic pathways. This dual effect of tibolone explains it's positive clinical

effects on bone, vagina and brain, and

avoids stimulation of the endometrium and breast tissue.

PMID: 11384882 [PubMed - indexed for MEDLINE]

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Shirley takes 2.5 mg of tibolone a day which has been shown to:

1)Treats climacteric symptoms

2) Has beneficial effects on cardiovascular parameters

3) Enhances mood and libido

4) Has a low incidence of breast tenderness

5) Does not stimulate the endometrium

6) Treats vaginal atrophy

7) Does not increase mammographic density

8) Prevents postmenopausal bone loss

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Good Health & Long Life,

Greg ,

http://www.ozemail.com.au/~gowatson

gowatson@...