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Pregnancy and lactation associated osteoporosis(PLO)is a rare disorder for women during pregnancy, the post-partum period, or while breastfeeding. It still remains unknown factors in its pathogenesis. That makes it there is no evident strategy for PLO now. In most cases, bone mineral density(BMD)of PLO patients spontaneously recovers after giving lactation up. On the other hand, patients with severe cases sometimes need bone specific therapy. There are some reports that show bisphosphonate, teriparatide and/or denosumab are effective on PLO cases. When the patients have wishes for having babies, we have to pay attention if the prescription effect on next pregnancy.

Development of bone metabolism markers began about 35 years ago. Current by the osteoporosis and bone metabolism diseases diagnosis and treatment efficacy. In childhood and adolescence, bone formation and resorption were increased, but formation rate was exceeded resorption rate. To keep strength of bone, bone formation and resorption are balanced(remodeling)in the period of maturity, Bone mineral density greatly decreases and biochemical markers of bone turnover markedly increase in postmenopausal women, indicating accelerated bone remodeling because of estrogen withdrawal. On the other hand, pregnancy and breastfeeding affect bone metabolism. So, we gynecologists should be careful about bone health with understanding characteristic of bone metabolism markers.

Selective estrogen receptor modulators (SERMs) have the potential to provide the skeletal benefits of estrogen without the increased risk of uterine and breast cancer. Raloxifene, second generation SERM has been approved for the prevention and treatment of post-menopausal osteoporosis. Bazedoxifene, third generation SERM acts as a tissue selective estrogen antagonist or agonist. These SERMs inhibited bone turnover and prevented bone loss caused estrogen deficiency. Furthermore, these SERMs did not affect the uterine endometrial thickness and reduced serum cholesterol. These data suggest that SERMs are potential drug for the prevention of osteoporosis in postmenopausal women.

Measurement of the bone mineral density have shown that lactating women had 1 to 3% decrease in bone mineral density. Post pregnancy osteoporosis is rare condition that causes fragile fracture mostly in vertebrae. The bone loss in lactating women is caused by calcium loss, decrease in estrogen level, and increase in PTHrP (parathyroid hormone related protein) level. Some data have shown that extended lactation and amenorrhea had an association with the degree of bone loss. Mostly, the bone loss of the lactating women recovers to the baseline level, soon after the weaning, and there is no long term effect. Post pregnancy osteoporosis should be concerned, when we see a lactating woman with fragile fracture of the vertebrae.

Selective estrogen receptor modulators (SERMs) have the potential to provide the skeletal benefits of estrogen without the increased risk of uterine and breast cancer. Raloxifene, second generation SERM has been approved for the prevention and treatment of osteoporosis. Bazedoxifene (BZA, TSE-424Z), novel SERM, acts as a tissue selective estrogen antagonist or agonist. Bazedoxifene inhibited bone turnover and prevented bone loss caused estrogen deficiency. Furthermore, this SERM did not affect the uterine endometrial thickness and reduced serum cholesterol. These date suggest that Bazedoxifene is novel potential drug for the prevention of osteoporosis in postmenopausal women.

Selective estrogen receptor modulators (SERMs) have the potential to provide the skeletal benefits of estrogen without the increased risk of uterine and breast cancer. Raloxifene, second generation SERM has been approved for the prevention and treatment of osteoporosis. Lasofoxifene (LAS) and bazedoxifene (BZA, TSE-424), novel SERMs, act as a tissue selective estrogen antagonist or agonist. These novel SERMs inhibited bone turnover and prevented bone loss caused estrogen deficiency. Furthermore, these SERMs did not affect the uterine endometrial thickness and reduced serum cholesterol. These date suggest that LAS and TSE-424 are novel potential therapy for the prevention of osteoporosis in postmenopausal women.

BMD is prescribed by the balance of bone resorption and osteogenesis. In osteoporosis, this balance collapses according to a certain cause, bone loss starts as a result because bone resorption exceeds osteogenesis. Since a bone turnover marker shows the bone metabolism at the time of measurement quantitatively, it is thought that the change in BMD is reflected. Therefore, it is in predicting bone reduction of the future and fast bone loser identifying is expected by measuring bone turnover markers. Reduction of bone density is large in high turnover of bone metabolism, and it is shown clearly by recent research that the risk of fracture goes up. There is the necessity for evaluation of the bone turnover markers which made fracture the end point also in Japan.

Both onset and cessation of menstruation have strong genetic inclination. We aimed to identify genetic factors influencing the onset of menarche and natural menopause in a Japanese population by investigating the polymorphisms of estrogen receptor-alpha and estrogen-metabolizing enzyme genes. Three hundred seventeen postmenopausal Japanese women, aged 46 yr and over, were enrolled in this study under informed consent. Genomic DNA was extracted from peripheral leukocytes, and PCR-based restriction fragment length polymorphism assays were used to determine estrogen receptor-alpha: PvuII, XbaI, and estrogen-metabolizing enzymes; CYP17, estrogen biosynthesis (high activity, A2/A2, CYP1A1), hydroxylation (high inducibility, vt/vt, and COMT), inactivation (low activity, L/L) genotypes. There were no significant differences in ages at menarche and natural menopause or years of menstruation among each PvuII or XbaI genotype and seven combinations of PvuII and XbaI genotypes. We found that ages at menarche in women with A1/A2 (higher activity of CYP17; 13.6 +/- 1.2 yr) were significantly earlier than in those with A1/A1 (lower activity of CYP17; 14.1 +/- 1.3 yr). There were no significant differences in age at natural menopause and years of menstruation among each CYP17, CYP1A1, or COMT genotype. The small sample size of each combination of estrogen-metabolizing genotypes made it impractical to evaluate the effects of the interdependency of each genotype, including extreme genotype categories such as A2/A2L/Lvt/vt vs. A1/A1H/Hwt/wt genotypes, on ages at menarche and/or natural menopause. The results suggest that the estrogen-metabolizing CYP17 genotype influences age at menarche in healthy postmenopausal Japanese women.