Bone disease

Published on 01/03/2015 by admin

Last modified 22/04/2025

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Bone disease

The finding that a patient has hypercalcaemia or hypocalcaemia does not imply that there will be marked bone changes. Conversely, severe bone disease can occur whilst serum calcium levels appear quite normal. The main bone diseases are:

osteoporosis

osteomalacia and rickets

Paget’s disease.

Bone metabolism

Bone is constantly being broken down and reformed in the process of bone remodelling (Fig 38.1). The clinician looking after patients with bone disease will certainly need to know to what extent bone is being broken down, and, indeed, if new bone is being made. Biochemical markers of bone resorption and bone formation can be useful in assessing the extent of disease, as well as monitoring treatment.

Fig 38.1 Bone remodelling.

Hydroxyproline, from the breakdown of collagen, can be used to monitor bone resorption. However, urinary hydroxyproline is markedly influenced by dietary gelatin. Better markers of resorption are required. One candidate would seem to be another collagen degradation product: the fragments of the molecule containing the pyridinium cross-links. Deoxypyridinoline is one such cross-link that is specific for bone, and not metabolized or influenced by diet.

The activity of the enzyme alkaline phosphatase has traditionally been used as an indicator of bone turnover. The osteoblasts that lay down the collagen framework and the mineral matrix of bone have high activity of this enzyme. Increased osteoblastic activity is indicated by an elevated alkaline phosphatase activity in a serum specimen. Indeed, children who have active bone growth compared with adults have higher ‘normal’ alkaline phosphatase activity in serum. However, alkaline phosphatase is also produced by the cells lining the bile canaliculi and is a marker for cholestasis. The bone isoenzyme of alkaline phosphatase may be measured, but there is need for a more specific and more sensitive marker.

Osteocalcin meets some of these requirements. It is synthesized by osteoblasts and is an important non-collagenous constituent of bone. Not all of the osteocalcin that an osteoblast makes is incorporated into the bone matrix. Some is released into plasma, and provides a sensitive indicator of osteoblast activity. The test is available in specialized laboratories.

Common bone disorders

Osteoporosis

Osteoporosis is the commonest of bone disorders and is discussed separately on page 78.

Osteomalacia and rickets

Osteomalacia is the name given to defective bone mineralization in adults (Fig 38.2). Rickets is characterized by defects of bone and cartilage mineralization in children. Vitamin D deficiency was once the most common reason for rickets and osteomalacia, but the addition of vitamin D to foodstuffs has reduced the condition except in the elderly or house-bound, the institutionalized, and in certain ethnic groups. Although elderly Asian women with a predominantly vegetarian diet are particularly at risk, it should be noted that there appears to be a resurgence of rickets and osteomalacia in the white population of lower socio-economic status, due to poor diet and limited exposure to sunlight. Vitamin D status can be assessed by measurement of the main circulating metabolite, 25-hydroxycholecalciferol, in a serum specimen. The metabolism of vitamin D is shown in Figure 38.3.

Fig 38.2 Bone biopsy showing normal (left) and osteomalacic (right) bone.

Fig 38.3 The main steps in the metabolism of vitamin D.

In severe osteomalacia due to vitamin D deficiency, serum calcium will fall, and there will be an appropriate increase in PTH secretion. Serum alkaline phosphatase activity will also be elevated.

The bony features of osteomalacia and rickets are also shared by other bone diseases (see later).

Paget’s disease

Paget’s disease is common in the elderly and characterized by increased osteoclastic activity, which leads to increased bone resorption. Increased osteoblastic activity repairs resorbed bone, but the new bone is laid down in a disorganized way. The clinical presentation is almost always bone pain, which can be particularly severe. Serum alkaline phosphatase is high, and urinary hydroxyproline excretion is elevated. These provide a way of monitoring the progress of the disease. Although a viral cause for Paget’s disease has been proposed, the aetiology remains obscure.

Other bone diseases

Examples include:

Vitamin-D-dependent rickets, types 1 and 2. These are rare bone diseases resulting from genetic disorders leading to the inability to make the active vitamin D metabolite, or from receptor defects that do not allow the hormone to act.

Tumoral calcinosis. This is characterized by ectopic calcification around the joints.

Hypophosphatasia. This is a form of rickets or osteomalacia that results from a deficiency of alkaline phosphatase.

Hypophosphataemic rickets. This is believed to be a consequence of a renal tubular defect in phosphate handling.

Osteopetrosis. This condition is characterized by defective bone resorption.

Osteogenesis imperfecta. Brittle bone syndrome is an inherited disorder which occurs around once in every 20 000 births.

Diagnosis of these and other rare conditions may require help from specialized laboratories.

Biochemistry testing in calcium disorders or bone disease

The role of the routine biochemistry laboratory in diagnosis and treatment of patients with calcium disorders and bone disease is to provide measurements of calcium, albumin, phosphate and alkaline phosphatase in a serum specimen as first line tests. Follow-up tests that may be requested include:

PTH

magnesium

urine calcium excretion

25-hydroxycholecalciferol

urine hydroxyproline excretion

osteocalcin.

Characteristic biochemistry profiles in some common bone diseases are shown in Table 38.1.

Table 38.1

Biochemical profiles in bone diseases

Disease	Profile
Bone metastases	Calcium may be high, low or normal
	Phosphate may be high, low or normal
	PTH is usually low
	Alkaline phosphatase may be elevated or normal
Osteomalacia/rickets	Calcium will tend to be low, or may be clearly decreased
	PTH will be elevated
	25-hydroxycholecalciferol will be decreased if the disease is due to vitamin D deficiency
Paget’s disease	Calcium is normal
	Alkaline phosphatase is grossly elevated
Osteoporosis	Biochemistry is unremarkable
Renal osteodystrophy	Calcium is decreased
	PTH is very high
Osteitis fibrosa cystica (primary hyperparathyroidism)	Calcium is elevated Phosphate is low or normal PTH is increased, or clearly detectable and thus ‘inappropriate’ to the hypercalcaemia