Primary osteoporosis in postmenopausal women

Abstract

World Health Organization (WHO) defines natural menopause as at least 12 consecutive months of amenorrhea not due to physiologic and pathologic causes. Statistics show that the mean age of natural menopause is 51 years in industrialized nations, compared to 48 years in poor and non-industrialized nations.1 With the average life span extended to 70 years, most women will spend more than one third of their life time beyond the menopausal transition. Besides, the proportion of menopausal women is rising since the aging population is expanding rapidly. Thus, the health: of menopausal women becomes a prime concern worldwide. Menopause is a natural physiological phenomenon resulting from primary ovarian failure secondary to apoptosis or programmed cell death. Ovarian function declines with age. The onset of menopause features the decreasing production of estradiol, as well as increasing levels of follicle-stimulating hormone (FSH). During the menopausal transition period, women will experience a number of bothersome symptoms, such as hot flashes, night sweats, vaginal atrophy and dryness, dyspareunia, sleep disturbance, and mood swings. Besides these, osteoporosis is the most prevalent disease in menopausal women, and is strongly associated with low quality of life and we concentrate on postmenopausal osteoporosis in this review. Osteoporosis, a multifactorial systemic skeletal disease, is characterized by low bone mineral density (BMD) and micro-architectural deterioration of bone tissue resulting in bone fragility.2 BMD measured by dual X-ray absorptiometry is the gold standard to diagnose osteoporosis. According to WHO criteria, osteoporosis is defined as the T-score of less or equal to 2.5 and osteopenia as the T-score between 1.0 and 2.5. The femoral neck and lumbar spine are recommended as the anatomic region of interest.3 BMD decreases with age, thus primary osteoporosis mainly occurs in women 10–15 years after menopause and elderly men around 75–80 years old. With an expanding aging population, osteoporosis and osteoporosis-related fractures are fast becoming important public health issues that are a considerable economic burden on health service resources. The achievement of peak bone mass is important to bone health, and plays a vital part in preventing osteoporosis and subsequent fractures in later years. It is reported that hip fractures could be reduced by 30% with an increase in peak bone mass of 10%.2 Bone mass accretion starts from childhood and continues into adulthood, and peak bone mass can be achieved in the mid-twenties for spine and hip while other bones, such as the radius, reach a peak at age of 40 years. After that, bone mass normally declines. By the age 70 years, bone mass has decreased by 30–40%.4 The main determinant of the peak bone mass is genetic factors. Studies found several genetic variants which are related to bone mass, including low-density lipoprotein receptor related protein 5 (LRP5), osteoprotegerin (OPG), sclerostin (SOST), oestrogen receptor 1, and the receptor activator of NF-κB (RANK) pathway genes.5 It has been found that hormone status regulates bone mass accretion, especially that of estrogen. Other factors including nutrition, smoking and exercise may also play a role in the process of the peak bone mass accumulation.6, 7 Healthy bone requires continuous remodeling which is pivotal for bone density maintenance. It is estimated that nearly 10% of the bone is updated by this process every year.8 Osteoclasts (bone resorbing cells) and osteoblasts (bone forming cells) are two kinds of cells that essentially form the bone multi-cellular unit, coordinating well to regular the balance of bone resorption and bone formation. The normal bone remodeling process consists of five phases: the resting phase, the activation phase, the resorption phase, the reversal phase, and the formation phase. Firstly, osteoclasts are recruited to the surface of the bone where they generate an acidic micro-environment between the cell and the surface of the bone, dissolving and resorbing the mineral content of the bone. After that, the osteoclasts undergo apoptosis and osteoblasts are recruited to the bone surface and then deposit collagen which is mineralized afterwards to form new bone.9 This process is regulated by several hormones, including parathyroid hormone, calcitonin, 1,25(OH)2-vitamin D3, and estrogen. Estrogen affects bone through the following mechanisms: 1) lowering the sensitivity of bone mass to PTH (parathyroid hormone), thus reducing bone resorption, 2) increasing the production of calcitonin, thus inhibiting bone resorption, 3) accelerating calcium resorption by the intestine, 4) reducing the calcium excretion from the kidney, and 5)estrogen can also have direct effects in the bone since there are estrogen receptors.10 At menopause the normal bone turnover cycle is impaired by estrogen deficiency. This may be due to the presence of estrogen receptors in osteoclast progenitor