Drugs and the musculoskeletal system

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.

Fig. 20.1

The sequence of events in the bone remodelling cycle and the sites of action of drugs.

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 .

Fig. 20.2

Calcium homeostasis and the effects of drugs.


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

  • Osteoporosis : increased fragility resulting from distortion of the microarchitecture of bone. Main causes are postmenopausal oestrogen deficiency, excessive use of glucocorticoids or thyroxine.

  • Rickets : defective bone mineralization caused by vitamin D deficiency.

  • Hypocalcaemia : caused by hypoparathyroidism or vitamin D deficiency.

  • Hypercalcaemia : caused by hyperparathyroidism and some cancers.

  • Hyperphosphataemia : caused by renal failure.

Drugs used to treat disorders of bone metabolism


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.

Mar 31, 2020 | Posted by in PHARMACY | Comments Off on Drugs and the musculoskeletal system

Full access? Get Clinical Tree

Get Clinical Tree app for offline access