Female obesity and osteoporosis

18.1

Introduction

• 1.

  Obesity and osteoporosis are two important problems affecting global health with a high impact on both mortality and morbidity.

• 2.

  Both have multifactorial aetiologies, including genetic and environmental components, with potential interactions between them.

• 3.

  Obesity is a condition of excessive body fat due to an imbalance when energy intake exceeds energy expenditure over a prolonged period.

  • a.

    In healthy adults, body weight is tightly regulated by several environmental, nutritional, and hormonal factors.

  • b.

    Postmenopausal women often show increased body weight, likely due to a decrease in basal metabolism, alteration of hormonal levels, and reduced physical activity.

  • c.

    They are often affected by hypertension, dyslipidaemia, diabetes mellitus (DM), and cardiovascular disease and also have an increased risk of developing some cancers.

• 1.

  Osteoporosis is a metabolic bone disease that is characterised by excessive skeletal fragility (due to a reduction in both bone quantity and quality) leading to an increased risk of developing spontaneous and traumatic bone fractures and even death.

  • a.

    It is characterised by a reduction in bone mass; it is typically defined in an individual with a bone mineral density (BMD) T-score that is 2.5 or more SD values below normal (T-score −2.5 or less).

  • b.

    Normal aging is associated with a high incidence of osteoporosis and bone marrow adiposity. Bone remodelling and adiposity are both regulated through the hypothalamus and sympathetic nervous system. Adipocytes (the cell for storing energy) and osteoblasts (the bone from a common progenitor)—the mesenchymal stem cell.

• 2.

  Interestingly, obese women have always been considered protected against osteoporosis.

  • a.

    Increased mechanical loading, associated with increased body weight, contributes to increases in bone mass.

  • b.

    One potential problem with these phenotypic studies is that the correlation between body weight (or BMI) and bone mass may not necessarily represent a correlation between obesity per se and osteoporosis, because it is excessive fat mass rather than total body weight that defines obesity.

  • c.

    Body weight is a heterogeneous phenotype consisting of fat, lean muscle, and bone mass. Fat mass accounts for approximately 16% and 25% of total body weight in normal-weight men and women, respectively; the majority of the remaining body composition is lean mass.

  • d.

    Conclusions from studies about the relationship between obesity and bone mass may be confounded by the mechanical loading effects of total body weight on the skeletal system.

18.2

Normal bone metabolism

Osteoblasts, osteoclasts, and osteocytes are the main cells of the bone.

• 1.

  Osteoblasts are nonproliferative bone building cells that originate from osteoblast progenitor cells and aid in the formation of the bone matrix by secreting osteoid, a substance responsible for bone mineralisation. It plays the most important role in bone formation

• 2.

  Osteocytes (mature osteoblast) are unable to divide and no longer secrete matrix components.

• 3.

  Osteoclasts originate from macrophage monocyte cell lineage and participate in bone resorption, ultimately leading to decreased bone mass.

• 4.

  Preosteoblasts express receptors for different types of growth factors, pro-inflammatory cytokines, and hormones, including bone morphogenic proteins, Wnt, transforming growth factor-beta, parathyroid hormone (PTH), interleukin-6 (IL-6), 5-HT, insulin/insulin-like growth factor, and tumour necrosis factor (TNF).

• 5.

  Binding of these ligands with their receptors induces the activation of different types of transcription factors responsible for osteoblast differentiation, maturation, and survival.

18.3

Epidemiology of osteoporosis and obesity

• 1.

  Osteoporosis has become a significant health problem as approximately 200 million people worldwide are estimated to have osteoporosis.

  • a.

    There are estimated 10 million aged more than 50 years in the United States with osteoporosis.

  • b.

    In a Brazilian study, the prevalence of fragility fracture in women and men aged higher than 40 years was 15.1% and 12.8%, respectively was reported.

• 2.

  The WHO’s World Health Statistics (2015) shows the obesity rate among adults in Europe is 21.5% in males and 24.5% in females.

• 3.

  It is projected that 60% of the world’s population, that is, 3.3 billion people, could be overweight (2.2 billion) or obese (1.1billion) by 2030 if recent trends continue.

• 4.

  Age and female gender increase the risk of developing both obesity and osteoporosis.

  • a.

    Age-related changes in body composition, metabolic factors, and hormonal levels after menopause, accompanied by a decline in physical activity, may all provide mechanisms for the propensity to gain weight.

  • b.

    Increase in fat mass often characterised by replacement of lean mass (LM) by adipose tissue.

  • c.

    The process of bone loss begins soon after menopause due to increased bone resorption by osteoclasts that exceed bone formation by osteoblasts.

  • d.

    Osteoblast function declines with aging, determining the imbalance between bone resorption and bone formation.

• 5.

  Premenopausal women with increased central adiposity had poorer bone quality and stiffness and markedly lower bone formation.

• 6.

  Most recent studies have reported that BMD appears to be a better long-term predictor of death than blood pressure or cholesterol.

18.4

Relationship between fat and bone: epidemiologic and clinical observations

• 1.

  The most powerful determinant of fracture risk is the amount of bone in the skeleton, as defined by either BMD or BMC

  • a.

    Extensive data have shown that high body weight or BMI is correlated with high BMD or BMC and a decrease in body weight leads to bone loss.

  • b.

    There is also evidence to support the view that fat mass, a component of total body weight and one of the most important indices of obesity, has a similar beneficial effect on increasing bone mass, thereby reducing the risk of osteoporosis.

  • c.

    In normal pre- and postmenopausal women, total body fat was positively related to BMD throughout the skeleton, and this effect was found in both White and Japanese subjects

  • d.

    Study showed that “rapid” bone losers had significantly lower fat mass than the “slow” bone losers.

• 2.

  However, in contrast to the abovementioned reported results, other independent groups have shown that excessive fat mass may not protect against decreases in bone mass.

  • a.

    In a large-scale study of Chinese and White subjects, when the mechanical loading effect of total body weight was statistically removed, then fat mass was negatively correlated with bone mass, thus suggesting that fat mass actually has a detrimental effect on bone.

  • b.

    A study conducted on evaluation of BMD in individuals with high body mass index has shown that obese patients have a significant reduction in bone mineral mass for age and BMI. It also showed the evidence that morbid obesity may not be considered a protective factor against osteoporosis in both female and male population.

• 3.

  Evidence from environmental factors and medical interventions also support an inverse correlation between fat mass and bone mass.

  • a.

    Physical exercise increases bone mass while reducing fat mass.

  • b.

    Consumption of milk which is a good source of highly absorbable calcium has been shown to increase peak bone mass at puberty, slow bone loss, and reduce the incidence of osteoporotic fractures in the elderly.

  • c.

    Menopause has also been associated with increased bone loss, increased fat mass, and decreased LM.

  • d.

    Hormone replacement therapy is an effective means of attenuating loss of LM and bone and reversing menopause related obesity in postmenopausal women.

  • e.

    Osteoporosis and obesity are side effects of treatment with gonadotropin-releasing hormone agonists.

  • f.

    The clinical use of glucocorticoids has been shown to cause decreased bone mass and an increase in central obesity.

• 4.

  The finding that all of these interventions have opposite effects on fat vs. bone mass supports the concept that there is an inverse correlation between fat and bone mass and that fat does not have a protective effect on the bone.

• 5.

  LM is the strongest predictor of BMD at all sites. It is important that LM should also be the target for improvement when considering prevention and/or management of osteoporosis.

18.5

Hormonal effect of obesity and osteoporosis