One in three women and one is 12 men over the age of 50 years have low bone density or osteoporosis. It is the major factor for the 70 000 hip, 50 000 wrist and 40 000 spinal fractures seen annually in the UK. As discussed earlier, postmenopausal osteoporosis represents a major public health issue. Osteoporosis has been defined as ‘a disease characterized by low bone mass and micro-architectural deterioration of bone tissue, leading to enhanced bone fragility and a consequent increase in fracture risk’. The development of osteoporosis depends upon both the peak bone mass attained and its subsequent rate of loss. Peak bone mass is achieved in early adulthood and is largely (80%) genetically determined. This has been confirmed in studies comparing bone mass in twins and in studies of racial groups that have migrated. To some extent, peak bone mass is influenced by diet, exercise, alcohol consumption, smoking, drugs (e.g., corticosteroids, contraceptive pills, liver enzyme inducers), parity and the presence or absence of estrogens. Estrogens seem to have a central role in regulating bone mass and estrogen-deficient states such as anorexia nervosa, secondary amenorrhea due to strenuous exercise, use of luteinizing hormone-releasing hormone (LHRH) analogs and the menopause have all been shown to lead to bone loss.

The development of osteoporosis results from an imbalance between bone resorption and bone formation and also depends on the peak bone mass. Loss of gonadal function and aging are the two most important factors. Starting around the fourth or fifth decade of life, men and women lose 0.3-0.5% of their bone mass every year. This is increased in women by up to ten-fold in the early years following surgical or natural menopause, due to an increase in bone turnover and bone resorption in excess of bone formation. Women may eventually lose up to 50% of their cancellous bone and 30% of their cortical bone. The speed of bone loss in later life decreases but continues inexorably into old age. The quality of bone is impaired, because the bone loss leads to disruption and perforation of the bone trabeculae which provide strength. After the trabeculae are disrupted treatment does not lead to their restoration, but merely thickens the remaining bone. The lifetime risk of osteoporotic fracture for women aged 50 is between 30 and 40%.

There are several reasons for this gender difference. Women have a lower peak bone mass than men, lose more bone than men after the menopause and women fall more often than men. Women have lower muscle mass and lower agility to prevent the consequences of falls.

Currently, bone density is measured using DXA scanning. The method is accurate and reproducible with a margin of error of between 0.5 and 1%. Importantly, because many interventions increase bone density between 0.5 and 3% per year, one year of treatment may not be enough to show treatment-related changes in the bone density. Bone density varies across different ethnic groups and geographically and therefore there should be separate reference ranges for different racial groups. The mean and standard deviation (SD) are established by measuring bone density in healthy young women. One SD decrease in bone density leads to doubling of the risk of fracture. The DXA scan results are expressed in two ways, as T-scores and Z-scores. Both scores are the standard deviation by which an individual bone density differs from a reference group. T-scores represent the bone density of the individual compared with the mean value of young healthy controls, while Z-scores represent the bone density of the individual compared to the mean value of their own age group. In our practice, we tend to use the T-score (young healthy controls) to assess bone density up to the age of 75. It can be argued that using the T-score results in too many women being classified with low bone density or osteoporosis. However, we think that such an argument is not in line with the measurement of the ventricular ejection fraction of the heart or the measuring of blood pressure, for example, and does little to increase the awareness in women of their bone health. Bone density and osteoporosis have been linked via the following classification from the World Health Organization (WHO):

  1. (1) Normal bone density: mean ± 1 SD (T-score > -1);
  2. (2) Low bone mass (osteopenia): between 1 SD and 2.5 SD below the mean (-1 > T-score >-2.5);
  3. (3) Osteoporosis: 2.5 SD below the mean (T-score < -2.5);
  4. (4) Severe osteoporosis: 2.5 SD below the mean (T-score <-2.5) plus one or more fractures.

In the absence of screening for osteoporosis, a case-finding strategy is recommended.

Qualitative ultrasound is increasingly being used for bone density measurement. Studies show that there is good correlation between ultrasound assessment of the bone density and the risk of fracture. Qualitative ultrasound equipment is much cheaper than DXA scanning, requires no special room for installation and its maintenance is easier. As clinical data accumulate, it is likely that qualitative ultrasound will play a much bigger role in the future.

Another way of assessing fracture risk is by monitoring biochemical indices of bone turnover. There are two types of biochemical markers: of bone resorption and of bone formation. The markers for bone resorption are hydroxyproline and the pyridinium crosslinks with their associated peptides. The markers for bone formation are alkaline phosphatase (total and bone-specific), osteocalcin and the protocollagen propeptides of type I collagen. In a state of predominant bone resorption, the markers of resorption increase and with treatment they decrease. The markers of bone formation are low in osteoporoiss and increase with treatment. The markers of bone turnover connot be used alone for diagnosing osteoporosis but in conjuction with BMD measurement could improve fracture prediction in postmenopausal women. Bone markers are useful in monitoring the response to treatment in the early stages. Bone density measurement should be offered to those women who are at increased risk for osteoporosis (Table Risk factors for osteoporosis) or for monitoring the response to treatment.

Table Risk factors for osteoporosis

  • Family history of osteoporosis
  • Hip fracture in first-degree relative
  • Low body mass index (< 19 kg/m2)
  • Early menopause (under the age of 45 years) (prolonged periods of oligo-amenorrhea during the reproductive years)
  • Smoking
  • Alcoholism
  • Low-calcium diet
  • Prolonged immobilization
  • Rheumatoid arthritis
  • Chronic liver disease
  • Malabsorption syndromes
  • Hyperthyroidism
  • Hyperparathyroidism
  • Chronic steroid use (prednisolone > 7.5 mg/day or equivalent)
  • Long-term (> 5 years) inhaled corticosteroids
  • Cushing’s syndrome
  • Radiographic evidence of osteopenia
  • Previous fracture of spine or wrist with minimal trauma

Treatment for osteoporosis

Estrogen therapy is now well established as a prophylaxis for the prevention of osteoporotic fracture and is also effective in women with established osteoporosis. Estrogens are thought to affect the bone both directly and indirectly. The direct actions include: (1) decreasing the number of resorption pits; (2) stimulating osteoblast activity to produce more type I collagen and transforming growth factor-(3; and (3) suppressing production of interleukin-1 and -6 and tumor necrosis factor-a. All of these actions promote bone resorption. Indirectly, estrogen is thought to: (1) reduce the level of parathyroid hormone; (2) enhance the absorption of calcium from the intestine; and (3) increase the secretion of calcitonin The minimum daily estrogen doses associated with bone preservation in early postmenopausal women are 0.625 mg of CEE, 1 mg of estradiol and 25 ug of transdermal estradiol. Apart from estrogen, there are a number of strategies which are useful in combating this scourge in older women, with bisphosphonates, calcium and vitamin D, weight-bearing exercise, selective estrogen receptor modulators (SERMs), calcitonin (parathyroid hormone), sodium fluoride and testosterone all being employed. There is good evidence from controlled clinical trials in favor of these treatments, and this is summarized in Table Antifracture activity of the most frequently used treatments of postmenopausal osteoporosis as derived from placebo-controlled randomized trials. Advice regarding osteoporosis prevention and treatment should be individualized, according to the patient’s circumstances, bone density, preferences and beliefs.

Table Antifracture activity of the most frequently used treatments of postmenopausal osteoporosis as derived from placebo-controlled randomized trials

Drug Vertebral fracture Hip fracture
Hormone replacement therapy + + + ++
Alendronate + + + + +
Etidronate + + +
Risedronate + + + + +
Parathyroid hormone + + + 0
Raloxifene + + + 0
Calcitonin + 0
Fluoride + 0
Vitamin D + 0

+ + +, strong evidence; + +, good evidence; +, some evidence; 0, no evidence

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