Metabolic Bone Disease Primary Osteoporosis - pediagenosis
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Sunday, April 25, 2021

Metabolic Bone Disease Primary Osteoporosis

Metabolic Bone Disease Primary Osteoporosis
Clinical background
Osteoporosis is a common disease of the elderly, affecting over 2 million women in the UK, and associated with significant morbidity and mortality. It is characterized by ‘fragility fractures’, defined as a fracture occurring after a fall from standing height or less and it is estimated that 33% of women and 20% of men over the age of 80 will sustain a hip fracture due to osteoporosis. Other common sites for osteoporotic fractures include the spine and distal radius (Colles’ fracture) and it is estimated that the cost to the UK National Health Service and social services of treatment for osteoporotic fractures of the hip alone is in the order of £2.3 billion per annum. Primary osteoporosis in women is due to a combination of age and estrogen deficiency; the cause in men is less clear but probably includes age-related falls in both estrogen and androgen concentrations.
Osteoporosis occurs in the context of lifetime changes in bone density. Peak bone density in both males and females is achieved in the late 20’s and age-related bone loss begins at the start of the fifth decade. Peak bone mass is genetically determined and a major predictor of osteoporosis risk in later life. Other factors include sex hormone status, nutrition, calcium and vitamin D status and levels of physical activity. Both men and women exhibit age-related bone loss from the fifth decade, but the process in women is accelerated during the menopause, reflecting the role of estrogen as a major factor in the maintenance of bone mineral density. Osteoporosis is diagnosed by assessing bone mineral density by means of dual-energy X-ray absorptiometry (DEXA) scanning. The patient’s score is measured according to standard deviation scores below normal peak bone mass.
A number of risk factors for osteoporosis have been identified and include age, sex, family history, Caucasian or Asian ethnicity, history of thyroid disease, cigarette smoking and excessive alcohol intake. The major risk factor for fractures in the elderly with osteoporosis is falling. Assessment of the patient should always include risk factors for falling such as visual impairment, cardiovascular disease with syncope, neuromuscular weakness and environmental hazards such as steps or poorly fitting carpets.
Therapeutic intervention may be offered as primary prevention to postmenopausal women, with significant risk factors depending upon their bone density and as secondary prevention following a fracture (see Chapter 55).

Estrogen and osteoporosis

Osteoporosis is loss of bone mass and is the most common metabolic bone disease. Gender, race, heredity, lifestyle and nutrition, particularly the degree of calcium intake during the period of peak bone growth, determine the incidence of osteoporosis (Fig. 54b). The main phases of bone mass change are:
(i) attainment of peak bone mass during postpubertal life and completion of bone mass consolidation between the ages of 20 and 30; (ii) commencement of bone loss between the ages of 30 and 40, which occurs equally in trabecular and cortical bone approximately 25% of bone is lost; and (iii) postmenopausal loss of bone, mainly trabecular (e.g. vertebral), secondary to estrogen loss (Fig. 54a).
People of African Caribbean origin have, on average, a higher peak bone mass than other ethnic groups. Mother daughter and twin studies suggest that hip fracture is more likely when there is a maternal history of osteoporosis, which may be accounted for by inheritance of polymorphic alleles of the vitamin D receptor gene in some populations. Nutritionally, an adequate intake of calcium by growing children and young adults is critical in the attainment of genetically determined peak bone mass, and calcium supplements have been shown to slow the rate of bone loss in the elderly, although it is not certain whether calcium supplements reduce the risk of fractures.
Exercise is an important factor in determining the rate of loss of bone mass with ageing in both men and women, and in both pre and postmenopausal women. The risk of hip fractures may be reduced through regular exercise, although it is not clear whether this is due to maintenance of adequate bone density or to maintenance of agility, balance and muscle strength. Smoking has been shown to increase the rate of metabolism of exogenous estrogens (for example in oral contraceptives), although it is not known if smoking has this metabolic effect on endogenously produced estrogens. A history of thyrotoxicosis is a risk factor for osteoporosis.
Recent studies have found evidence that 5-HT in the gut slows or may even stop phosphate uptake in the gut. This is being actively studied and could conceivably generate novel treatments to supplement mainstream treatments of osteoporosis.

Estrogen and osteoporosis
Osteoporosis through estrogen deficiency is not age-dependent; accelerated bone loss may occur in hypogonadal women of whatever cause. After menopause, there is an acceleration of bone resorption due to estrogen deficiency, detected at biopsy as increased activation frequency of basic multicellular units on bone and increased resorption surfaces. There is increased excretion of metabolites of collagen and bone and a moderate depression of PTH secretion. The coupling mechanism of remodelling is maintained, with significant increases in levels of serum alkaline phosphatase, osteocalcin and bone-specific alkaline phosphatase. All these are indices of high bone turnover rates. Estrogen dampens osteoclast function partly through inhibition of monocyte activation and of osteoblast activity through suppression of genes that express IL-1, IL-6 and TNF (Fig. 54c).
The onset of osteoporosis is often painless and insidious and, unless routine bone scans are done, the first symptoms are due to the fracture. Spinal fractures in particular may be painless, or present as persistent back pain that is relieved by bed rest and exacerbated by any weight-bearing action (Fig. 54d). Fracture healing brings remission from pain. With multiple compression fractures of the spine a sharply localized forward angulation, called kyphosis, may result. The deformity is caused by collapse of the anterior section of the vertebra. Appendicular osteoporotic fractures (fractures of the limb bones) are often characterized by fractures of the distal radius and the femoral neck.

Imaging studies and laboratory findings
Bone densitometry is a reliable diagnostic tool. It measures the total bone density or calcium content at the wrist, spine and hip. The margin of error is small (1–2%) and the radiation dose administered is a fraction of that given by X-ray. Other methods include quantitative computed topography, which is more precise for cancellous than for compact bone. X-rays are used but are less sensitive and can give false positives since over-pentetrated films may misrepresent a normal spine as osteopenic. Osteoporosis will not be detected by X-ray until approximately 35–55% of bone mass is lost.

Laboratory parameters
Osteocalcin and bone-specific alkaline phosphatase, markers of bone formation, may be raised. Hormonal indices in blood more often reflect age-related changes than any that might be associated with osteoporosis. Serum levels of 1,2,5(OH)2D may be lower in patients with osteoporosis but this is more likely to be due to the reduction observed with ageing, and explained by reduced renal mass. Overall, serum chemistry values are normal in patients with osteoporosis. Alkaline phosphatase levels are raised when there is bone healing after osteoporotic fractures.

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