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Metabolic Bone Disease Secondary Osteoporosis


Metabolic Bone Disease Secondary Osteoporosis
Introduction
Osteoporosis may occur as a secondary problem in patients with a range of endocrine and other disorders (Fig. 55a; Table 55.1). A high proportion of patients treated chronically with glucocorticoids develop osteoporosis. It may develop in patients immobilized for long periods, when bone resorption develops with consequent hypercalciuria and hypercalcaemia, especially in younger patients in whom bone turnover is normally rapid. Osteoporosis has been observed in astronauts, presumably due to the loss of gravitational effects, although the aetiology of this phenomenon is unknown. Hereditary disorders of collagen expression and metabolism may result in osteoporosis. These include Ehlers–Danlos syndrome, homocysteinuria and osteogenesis imperfecta.

The vast majority of patients with osteoporosis have the primary condition but causes of secondary osteoporosis should always be sought when undertaking clinical assessment.
Glucocorticoids and osteoporosis Glucocorticoids, used to treat inflammatory disorders, cause osteoporosis, affecting predominantly the trabecular bone of the axial skeleton such that vertebral fractures are more common than those of the hip. Glucocorticoids cause osteoporosis through a wide variety of actions (Fig. 55b).
Direct actions. Glucocorticoids directly inhibit the replication of osteoblast lineages and the biosynthesis of new osteoblast cells and they induce apoptosis of osteoblasts, partially through their interactions with growth factors such as the insulin-like growth factors. In addition, glucocorticoids may directly decrease synthesis of osteocalcin, a component of bone matrix, and stimulate the synthesis of collagenase-3, which breaks down collagen types I and II, essential building blocks of bone. Furthermore, glucocorticoids stimulate osteoclast activity directly, and possibly indirectly, via secondary hyperparathyroidism.
Indirect actions. Glucocorticoids inhibit calcium absorption from the GIT and increase renal excretion, which may contrib- ute to the development of secondary hyperparathyroidism. Glucocorticoids are associated with decreased plasma levels of estrogens and testosterone by suppressing adrenocorticotrophic hormone (ACTH) secretion from the anterior pituitary gland, thus resulting in suppression of adrenal androgen production. Luteinizing hormone production is decreased with consequent lowering of both estradiol and testosterone production in women and men respectively. Glucocorticoids also inhibit growth hormone production. Patients with Cushing’s syndrome, which is associated with excessive adrenal activity, may also be at risk of osteoporosis and fractures.
Glucocorticoid therapy is a major cause of rapid bone loss and primary preventive therapy with bisphosphonates should be prescribed for every patient about to start a course of steroid therapy for more than 3 months.

Metabolic Bone Disease: III Secondary Osteoporosis

Other endocrine disorders
Hyperthyroidism can cause osteoporosis by the direct action of thyroid hormone on bone resorption, since thyroid hormone is normally associated with high bone turnover. Fractures are uncommon in hyperthyroidism due to prompt diagnosis and treatment. Postmenopausal women with osteoporosis and a history of hyperthyroidism are, however, at increased risk of hip fractures. Type 1 diabetes mellitus is associated with mild osteopenia of cortical bone, although there does not seem to be a high incidence of fractures in these patients. Patients with Type 2diabetes mellitus, on the other hand, usually have normal bone mass.

Heritable disorders
Several hundreds of mutations of the collagen Type 1 gene have been reported, some of which may result in defective osteoblast activity and result in brittle and fragile bones. Osteogenesis imperfecta, for example, is caused by a mutation of the gene which codes for Type 1 collagen, the main structural protein in bone matrix. Different phenotypes may produce anything from a relatively mild condition to one that is lethal to the embryo.

Immobilization and osteoporosis
Patients who are immobilized for prolonged periods, for example with neuromuscular disease or after spinal injuries, are risk of developing osteoporosis. Prolonged immobility in bed may reduce bone density by about 0.5% each month. Lumbar spine density may decrease at a rate of about 1% each week, resulting in anything up to a 50% loss of bone mass after a year. This is reversible, and mineralization of bone is initiated when the patient becomes ambulatory again.

Prevention and treatment of osteoporosis
Patients at risk from osteoporosis should be given suitable lifestyle advice to maintain adequate nutrition and normal body weight, to stop smoking and moderate excess alcohol intake and to take as much weight-bearing exercise as possible. Patients with established disease may benefit from hip-protectors if they are at risk of falling, plus suitable occupational therapy assessment and walking aids.
Estrogen replacement therapy at the menopause, with or without progestagens, has formed the mainstay of treatment in women to prevent postmenopausal bone loss. However, recent data from large observational studies have raised questions about the safety of HRT in women over 50 years in terms of the increased risk of breast cancer. Estrogen replacement should be offered to immediate women around the time of the menopause for symptomatic relief but it is no longer recommended as first-line therapy for the prevention of osteoporosis in women over 50 years. Younger women with premature ovarian failure continue to receive estrogen up to 50 years of age.
Therapeutic intervention as primary prevention may be offered to postmenopausal women with significant risk factors depending upon their bone density. The bisphosphonates etidronate, alendronate and risendronate have all been shown to prevent bone loss in the spine and hip, both in healthy women at the menopause and in older patients with established osteoporosis. Alendronate and risendronate have also both been shown to reduce the fracture rate in women with osteoporosis. Strontium ranelate may be offered to women intolerant of bisphosphonates. Following a fracture, the same drugs may be offered or alternatives such as raloxifene considered. Teriperatide, a PTH analogue, may be used where no other drug is tolerated or effective.
Glucocorticoid-induced osteoporosis should be prevented by primary prevention in patients starting treatment by the coprescription of a bisphosphonate. In patients who have been on prednisolone 7.5 mg daily or equivalent for 6 months or more, a dual emission X-ray absorptiometry (DEXA) scan will establish the bone mineral density and treatment can be given accordingly.