Introduction To Osteoporosis
Osteoporosis is a common metabolic bone disease characterized by a loss of bone mass and strength, a deterioration of bone structure and an increased risk of fractures. Bone strength is a reflection of bone mineral density (BMD) and bone quality. Approximately 10% of the world population suffers from osteoporosis, and 30% of post-menopausal women.
A loss of bone mass with progressing age is expected from the age of 30 as changes in the bone remodelling cycle lead to fragility. The pathophysiology of osteoporosis is linked to a lack of homeostasis between bone formation and bone loss during the continuous remodelling of bone tissue. Bone formation is greater than bone resorption during childhood growth, in early adulthood these processes are relatively equal, and with progressive age bone loss is greater than bone formation, leading to the risk of osteoporosis.
Primary bone cell types include osteoblasts (bone-forming) and osteoclasts (bone-degrading). Several factors are involved in bone remodelling that influence the activities of osteoblasts and osteoclasts.
The formation of osteoclasts depends on the presence of the receptor activator of NF-κB ligand (RANKL), whose expression leads to bone resorption through a cascade of regulatory enzymes and transcription factors. High levels of RANKL are observed in females at the onset of menopause, increasing osteoclast production and bone resorption. The RANKL pathway is modifiable by a variety of hormones and inflammatory cytokines that can influence osteoclast production.
Bone formation is influenced by the production of mature osteoblasts that secrete a matrix of type I collagen and non-collagenous proteins for mineralization. Vitamin D, calcium, and phosphate influence the mineralization of the bone matrix. Terminally differentiated osteoblasts within the mineralized matrix are referred to as osteocytes.
The major clinical significance of osteoporosis is the consequent fracture risk which is associated with increased mortality. An estimated 40% of patients with osteoporosis will experience a bone fracture; it is therefore important to identify individual risk of osteoporosis early in life in order to prevent debilitating fractures.
BMD is the amount of bone mass per unit volume or per unit area. Dual x-ray absorptiometry (DXA) scans are primarily used to assess BMD in the diagnosis of osteoporosis, with a T score of less than -2.5 indicating the presence of the disease. The T-score is the standard deviation of an individual’s BMD from the average for young healthy individuals. In addition, the fracture-risk assessment tool (FRAX) can be used to assess individual risk of sustaining a fracture.
Risk Factors For Osteoporosis
There are multiple risk factors that influence osteoporosis risk including both genetic and environmental factors – unchangeable and variable or preventable factors. In combination, these risk factors can contribute to a loss of bone mass, and ultimately osteoporosis.
Advanced age, the female sex, race and hormone imbalance have all been associated with osteoporosis risk. Dietary factors such as protein, Vitamin D and calcium intake as well as participation in exercise have also been linked to the risk of disease.
Smoking is associated with a reduction in bone resistance to mechanical stress and resistance due to an alteration in the microarchitecture of trabecular bone, and has been identified as an independent risk factor for osteoporosis.
Excessive alcohol consumption has been negatively associated with bone remodelling and osteoblast production and activity, therefore influencing bone homeostasis. Some studies have however indicated that low alcohol consumption (0.5 – 1 drink per day) may have a positive effect on BMD with certain substances having an oestrogen-like stimulatory effect on bone.
Vitamin D deficiency is correlated with a wide range of diseases including osteoporosis, rickets, cardiovascular disease, autoimmune disease, multiple sclerosis and cancer. A growing awareness of the consequences of Vitamin D deficiency has led to an increase in Vitamin D testing amongst healthcare practitioners. Vitamin D plays an important role in calcium absorption and phosphate metabolism.
The two predominant forms of vitamin D are D2 (ergocalciferol) and D3 (cholecalciferol), both of which are available in small quantities from the diet, and in higher amounts from supplements. In humans the major source of Vitamin D is the endogenous production of the vitamin, prompted by skin exposure to the sun’s ultraviolet rays. Foods naturally high in vitamin D include egg yolk, fatty fish and fish liver oil.
Vitamin D produced through UV exposure or obtained in food undergoes two hydroxylation reactions within the liver and kidneys in order to convert it into a biologically active form (1,25-dihydroxycholecalciferol). These reactions lead to the production of the Vitamin D metabolites 25(OH)D and 1,25(OH)2D. Serum 25-hydroxyvitamin D (25[OH]D) should be measured in patients who are at risk for vitamin D deficiency, or where deficiency is expected.
Calcium is the most abundant mineral in the body and sufficient intake is essential in the prevention and treatment of osteoporosis. Calcium has an important role in supporting the structure and function of bone and teeth where the majority of calcium in the body is stored. Serum calcium is tightly regulated, therefore inadequate calcium intake will lead to bone breakdown as the body will use the stored calcium in bone in order to maintain other body functions.
Calcium can be predominantly obtained in dairy products such as milk, yoghurt and cheese. Other foods that are high in calcium include spinach, kale, okra, collard greens and soybeans.
Dietary sources of calcium are preferred, with supplementation only being considered in those individuals with inadequate dietary intake or at high risk for osteoporosis.
Recommended daily intake varies with age, however for adults 50 years or older the American College of Endocrinology and the American Association of Clinical Endocrinologists recommend a total intake of 1200 mg/day for disease prevention. This would be equivalent to 2 cups of milk, 1 cup of broccoli, a handful of almonds, and ½ tin of sardines. Dietary intake of magnesium is required for adequate calcium absorption. Magnesium rich food sources include nuts, spinach and wholegrains.
Caffeine intake interferes with intestinal calcium absorption and leads to an increase of calcium excretion through urine. Caffeine is also suggested to have a harmful effect on osteoblast proliferation and activity. Individuals at risk for osteoporosis, with a low BMD, or those who are genetically predisposed, may need to limit caffeine intake to 1-2 servings of caffeinated beverages per day.
An active lifestyle that includes regular (3-4 days/week) weight-bearing exercise is key in preventing osteoporosis. Activity stimulates the mechanoreceptors of the osteocytes to induce remodelling, the removal of damaged bone and synthesis of new bone. Hence a gradual decrease in BMD is observed in sedentary individuals.
A meta-analysis of 13 trials demonstrated a 2% improvement in BMD in post-menopausal women that exercised in comparison to those that do not exercise. In addition to improving BMD, weight-bearing and resistance exercise can also improve strength, posture and balance which may reduce the risk of falls resulting in fractures.
Bone Health PowerPoint Presentation
The Role of Exercises in Osteoporotic Fracture Prevention and Current Care Gaps. Where Are We Now? Recent Updates
European Guidance for the Diagnosis and Management of Osteoporosis in Postmenopausal Women