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IMS Menopause Live

Changes in bone resorption during the menopause transition

26 August 2013

Sowers and colleagues have investigated potential associations between changes in bone resorption during the menopause transition and reproductive hormones, body mass index (BMI) and ethnicity [1]. Urinary type I collagen N-telopeptide (NTX), estradiol, and follicle stimulating hormone (FSH) levels were measured annually for up to 8 years spanning the menopause transition in 918 African-American, Chinese, Japanese, or Caucasian women. Urinary NTX began to increase sharply about 2 years before the final menstrual period (FMP), reaching its peak level about 1–1.5 years after the FMP. NTX levels declined modestly from 2–6 years after the FMP but remained about 20% higher than before the menopause transition. The sharp rise in FSH occurred in conjunction with a sharp decline in estradiol and shortly after FSH levels began to increase rapidly. The mean increase in urinary NTX across the menopause transition was greatest in women with BMI < 25 kg/m2 and smallest in women with BMI > 30 kg/m2. Increases in NTX were greatest in Japanese women and smallest in African-Americans. These differences were attenuated, but not eliminated, when analyses were adjusted for covariates, particularly BMI. During the menopause transition, a decline in ovarian function beginning about 2 years before the FMP is followed by an increase in bone resorption and subsequently by bone loss. The magnitude of the increase in bone resorption is inversely associated with BMI. Ethnic differences in changes in bone resorption are attenuated, but not eliminated, by adjustment for BMI. Ethnic differences in BMI, and corresponding ethnic differences in bone resorption, appear to account for much of the ethnic variation in perimenopausal bone loss.

 

Comment

Hormones are essential for skeletal development and to maintain bone health. During the menopause transition, levels of estrogen decrease to one-tenth or less of what they had been previously. As a result, the hypothalamus stimulates the pituitary gland to increase ovarian activity to produce more FSH. Thus, the concentrations of FSH and luteinizing hormone (LH) in blood serum are increased by more than ten times their former values in the menopause transition phase [2].

Estrogen plays an important role in antagonizing the effect of parathyroid hormone to minimize bone loss. During the perimenopausal phase, there is an increase in bone resorption due to the decline in ovarian function. Similar studies to evaluate the effects of reproductive hormones on bone health have been carried out. Increased BMI is believed to confer protection against osteoporosis. There are enough epidemiological data available to show that BMI is correlated with high bone mineral density and that low BMI causes more bone loss [3].

In the menopause transition, the composition of bone marrow shifts to adipocyte cells and osteoclast activity is increased, resulting in resorption of bone [4]. Adipocytes and osteoblasts originate from a common progenitor, pluripotential mesenchymal stromal cells, and their differentiation is regulated through the peroxisome proliferator-activated receptor (PPAR)-γ pathway [5]. Activation of PPAR-γ drives the differentiation of mesenchymal stromal cells toward adipocytes over osteoblasts [6]. Adipocytes are important sources of estrogen production in postmenopausal women, and estrogen is known to inhibit bone resorption by osteoclasts. It has been proposed that increases in adipose tissue with increasing BMI in postmenopausal women result in increased estrogen production, osteoclast suppression, and a resultant increase in bone mass [7].

The present study shows that urinary FSH and LH are increased in women with low BMI and vice versa. Body mass index is not the only factor affecting bone resorption in the menopausal transition phase; other factors such as nutrition, smoking, medication, associated diseases, vitamin D deficiency, etc. should also be considered. Deficiency of vitamin D plays an important role in calcium absorption and stimulation of osteoblastic activity [8]. There may not be a correlation between increased BMI and bone resorption, because it is excess fat mass rather than total body weight that defines obesity. More studies are needed to evaluate the correlation between BMI and bone mass density. The outcome of these studies should be the reduction of fracture risk and not bone mass density alone in postmenopause because it is the fractures about which we are most concerned, so as to give postmenopausal women a good quality of life and not just years of life.

Alka Kumar

Gynaecologist and Wellness Consultant, Secretary Indian Menopause Society, Nagpur Chapter India, Director of Shalaka Hospital and Menopause Clinic, Nagpur, India

References

1.Sowers MR, Zheng H, Greendale GA, et al. Changes in bone resorption across the menopause transition: effects of reproductive hormones, body size, and ethnicity. J Clin Endocrinol Metab 2013;98:2854-63.

http://www.ncbi.nlm.nih.gov/pubmed/23666961

2. Sowers MF, Zheng H, McConnell D, et al. Follicle stimulating hormone and its rate of change in defining menopause transition stages. J Clin Endocrinol Metab 2008;93:3958-64

http://www.ncbi.nlm.nih.gov/pubmed/18647816

3. Paula FJ, Rosen CJ. Obesity, diabetes mellitus and last but not least, osteoporosis. Arq Bras Endocrinol Metabol 2010;54:150-7.

http://www.ncbi.nlm.nih.gov/pubmed/20485903

4. Zhao LJ, Liu YJ, Liu PY, Hamilton J, Recker RR, Deng HW. Relationship of obesity with osteoporosis. J Clin Endocrinol Metab 2007;92:1640-6.

http://www.ncbi.nlm.nih.gov/pubmed/17299077

5. Akune T, Ohba S, Kamekura S, et al. PPARgamma insufficiency enhances osteogenesis through osteoblast formation from bone marrow progenitors. J Clin Invest 2004;113:846–55.

http://www.ncbi.nlm.nih.gov/pubmed/15067317

6. Pei L, Tontonoz P. Fat’s loss is bone’s gain. J Clin Invest 2004;113:805–6.

http://www.ncbi.nlm.nih.gov/pubmed/15067310

7. Kameda T, Mano H, Yuasa T, et al. Estrogen inhibits bone resorption by directly +6inducing apoptosis of the bone-resorbing osteoclasts. J Exp Med 1997;186:489–95.

http://www.ncbi.nlm.nih.gov/pubmed/9254647

8. Zargar AH, Ahmad S, Masoodi SR, et al. Vitamin D status in apparently healthy adults in Kashmir Valley of Indian Subcontinent. Postgrad Med J 2007;83:713-16.

http://www.ncbi.nlm.nih.gov/pubmed/17989271

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