Bone metabolism
Bone is continuously remodelled throughout life, osteoclasts digesting it and osteoblasts laying down new bone ( Fig. 20.1 ). Endogenous factors influencing the process include parathormone (PTH, parathyroid hormone), the vitamin D family, calcitonin and various cytokines. Exogenous factors include diet, exercise and drugs. Oestrogens, in particular, inhibit bone digestion. These factors are closely related to the control of calcium ion (Ca 2+ ) homeostasis.
Calcium homeostasis
In many cells, calcium influx into the cytoplasm is involved in signal transduction in many cell types and so plasma Ca 2+ levels need to be controlled very precisely. Cytosolic [Ca 2+ ] is about 100 nmol/L and plasma [Ca 2+ ] is about 2.5 mmol/L. The factors controlling plasma [Ca 2+ ] are outlined in Fig. 20.2 .
Calcitonin
Calcitonin is produced by C cells in the thyroid follicles and its secretion is determined by plasma [Ca 2+ ]. Calcitonin decreases plasma [Ca 2+ ] ( Fig. 20.2 ).
Disorders of bone metabolism
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Osteoporosis : increased fragility resulting from distortion of the microarchitecture of bone. Main causes are postmenopausal oestrogen deficiency, excessive use of glucocorticoids or thyroxine.
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Rickets : defective bone mineralization caused by vitamin D deficiency.
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Hypocalcaemia : caused by hypoparathyroidism or vitamin D deficiency.
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Hypercalcaemia : caused by hyperparathyroidism and some cancers.
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Hyperphosphataemia : caused by renal failure.
Drugs used to treat disorders of bone metabolism
Bisphosphonates
Examples are disodium etidronate and alendronate.
These drugs prevent osteoclast-mediated bone resorption by inhibiting enzymes in the ruffled border ( Fig. 20.1 ). In addition, bisphosphonates are incorporated into the bone matrix and ingested by the osteoclasts promoting osteoclast apoptosis.
Bisphosphonates are given orally (milk impairs absorption) and 50% of the absorbed drug concentrates at sites of bone mineralization for a long period of time.
Unwanted effects
Gastrointestinal (GI) tract disturbances (alendronate can cause oesophagitis) and bone pain.
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