Carolina Aguiar Moreira Kulak

OSTEOPOROSIS AND LOW BONE MASS IN PREMENOPAUSAL AND PERIMENOPAUSAL WOMEN

OBJECTIVE To characterize the historical, clinical, and biochemical features of 111 young women (age, <55 years) referred for evaluation of osteoporosis or low bone mass. METHODS Women with a bone mineral density T score < or = -2.0 (N = 111) at one or more anatomic sites (by dual-energy x-ray absorptiometry) were assessed relative to anthropomorphic and biochemical characteristics and risk factors for osteoporosis. RESULTS Of 111 women with low bone mass or osteoporosis, 73 (66%) had identifiable causes of bone loss, of which estrogen deficiency (menopause, premenopausal estrogen deficiency) and conditions associated with estrogen deficiency (anorexia nervosa, cancer chemotherapy) were the most common. Prolonged use of glucocorticoids was the most common secondary cause of osteoporosis. Of 38 women with no identifiable cause of bone loss, 21 were premenopausal (mean age, 38 +/- 10 years [standard deviation]) and 17 were perimenopausal (mean age, 50 +/- 3 years). The mean lumbar spine T score was -2.18 +/- 1.0 in the premenopausal and -2.51 +/- 0.6 in the perimenopausal women. Nontraumatic fractures were reported by 42% of the premenopausal women and 18% of the perimenopausal women. A family history of osteoporosis was reported by 71% of the premenopausal and 47% of the perimenopausal women. CONCLUSION Most young women with osteoporosis or low bone mass had estrogen deficiency or another secondary cause of premature bone loss (or both). A subset of premenopausal and perimenopausal women, however, had no identifiable cause of bone loss. The strong family history of osteoporosis, especially in the premenopausal women, provides further support for current theories of a genetic predisposition to osteoporosis.

Bone histomorphometry: a concise review for endocrinologists and clinicians

Bone histomorphometry is a quantitative histological examination of an undecalcified bone biopsy performed to obtain quantitative information on bone remodeling and structure. Labeling agents taken before the procedure deposit at sites of bone formation allowing a dynamic analysis. Biopsy is indicated to make the diagnosis of subclinical osteomalacia, to characterize the different forms of renal osteodystrophy and to elucidate cases of unexplained skeletal fragility. Bone histomorphometric parameters are divided into structural and remodeling subgroups, with the latter being subdivided into static and dynamic categories. Metabolic bone disorders such as osteomalacia, hyperparathyroidism, hypothyroidism, osteoporosis and renal osteodystrophy display different histomorphometric profiles. Antiresorptive and anabolic drugs used for the treatment of osteoporosis also induce characteristic changes in the bone biopsy. Bone histomorphometry is an important research tool in the field of bone metabolism and provides information that is not available by any other investigative approach.

Skeletal microstructural abnormalities in postmenopausal women with chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is associated with osteoporosis and fragility fractures. The objectives of this study were to assess static and dynamic indices of cancellous and cortical bone structure in postmenopausal women with COPD. Twenty women with COPD who had not received chronic oral glucocorticoids underwent bone biopsies after double tetracycline labeling. Biopsies were analyzed by histomorphometry and µCT and compared with age‐matched controls. Distribution of the patients according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) was: Type I (15%), Type II (40%), Type III (30%), and Type IV (15%). Mean (±SD) cancellous bone volume (15.20 ± 5.91 versus 21.34 ± 5.53%, p = .01), trabecular number (1.31  ±  0.26 versus 1.77 ± 0.51/mm, p = .003), and trabecular thickness (141 ± 23 versus 174 ± 36 µm, p = .006) were lower in patients than in controls. Connectivity density was lower in COPD (5.56 ± 2.78 versus 7.94 ± 3.08/mm, p = .04), and correlated negatively with smoking (r = −0.67; p = .0005). Trabecular separation (785 ± 183 versus 614 ± 136 µm, p = .01) and cortical porosity (4.11 ± 1.02 versus 2.32 ± 0.94 voids/mm2; p < .0001) were higher in COPD while cortical width (458 ± 214 versus 762 ± 240 µm; p < .0001) was lower. Dynamic parameters showed significantly lower mineral apposition rate in COPD (0.56 ± 0.16 versus 0.66 ± 0.12 µm/day; p = .01). Patients with more severe disease, GOLD III and IV, presented lower bone formation rate than GOLD I and II (0.028 ± 0.009 versus 0.016 + 0.011 µm3/µm2/day; p = 04). This is the first evaluation of bone microstructure and remodeling in COPD. The skeletal abnormalities seen in cancellous and cortical bone provide an explanation for the high prevalence of vertebral fractures in this disease.

CHAPTER 43 – Secondary Osteoporosis

Osteoporosis is multifactorial in etiology, and is influenced by genetics, hormonal, nutritional, and lifestyle factors. Therefore, the impact of hyperthyroidism on bone loss and its long term consequences are variable, depending on the nature and severity of the thyroid disease, as well as on individual bone health and the presence of other risk factors for osteoporosis. The increased availability of bone densitometry and biochemical markers of bone remodeling has resulted in a greater understanding of thyroid related bone loss. The term primary osteoporosis is generally used to describe the progressive bone loss that occurs with aging, in both men and women, especially in postmenopausal women. Secondary osteoporosis may result from endocrine abnormalities, such as hyperthyroidism, hypogonadism, Cushings syndrome, and hyperparathyroidism. In addition, some chronic conditions, such as malabsorption, immobilization, hepatic, and renal disease can result in bone loss. Many drugs also cause secondary osteoporosis. This chapter reviews the impact of some of these more commonly encountered disorders of the skeleton, with specific emphasis on bone mineral density and parameters of bone remodeling.

Safety, Efficacy and Patient Acceptability of Bazedoxifene Acetate in the Management of Postmenopausal Osteoporosis

Many pharmacological agents are available for treatment of postmenopausal osteoporosis, including estrogen and the selective modulators of estrogen receptor (SERMS). Bazedoxifene is a third-generation SERM, which acts as estrogen agonist in bone and lipid metabolism and as an antagonist in the breast and endometrium. Studies demonstrated that bazedoxifene reduced significantly the risk of vertebral fractures. In a subgroup of patients at high risk (post-hoc analysis), a reduction of nonvertebral fractures risk was reported. Moreover, the combination of conjugated estrogens with bazedoxifene seems to offer an alternative to classical hormone therapy, improving the vasomotor symptoms and vaginal atrophy, without the use of a progestin. Bazedoxifene is a promising drug for the treatment and prevention of osteoporosis in postmenopausal women; however a safety concern regarding venous thromboembolic events is needed before starting treatment.