Rarer causes

These include inadequate alkaline phosphatase activity (hypophosphatasia), inhibition of mineralization by excess fluoride ingestion and abnormal bone matrix, for example in osteogenesis imperfecta or fibrogenesis imperfecta.

Box 26.1 Causes of osteomalacia

Vitamin Ddeficiency

Reduced synthesis, intake or absorption

Inadequate sunlight exposure

Malabsorption: small bowel disease (e.g. coeliac disease, inflammatory bowel disease), extensive bowel surgery, gastrectomy, pancreatic insufficiency

Reduced 25-hydroxylation of vitamin D

Liver disease

Anticonvulsants

Reduced 1α-hydroxylation

Chronic kidney disease

Hypoparathyroidism (reduced stimulation of vitamin D 1α-hydroxylation by PTH)

Vitamin D-dependent rickets type 1 (an autosomal recessive disorder caused by mutations in the gene encoding the enzyme 1α-hydroxylase)

Vitamin D-dependent rickets type 2 (an autosomal recessive disorder caused by mutations in the gene encoding the vitamin D receptor, resulting in target organ resistance to vitamin D)

Primary renal phosphate wasting

Type 2 renal tubular acidosis: Fanconi’s syndrome, multiple myeloma

Hereditary hypophosphataemic rickets (X-linked and autosomal dominant)

Oncogenic osteomalacia

Rarer causes

Abnormal bone matrix: osteogenesis imperfecta, fibrogenesis imperfecta

Hypophosphatasia (associated with periodontal disease)

Mineralization inhibitors: high doses of fluoride (e.g. in certain teas), aluminium, bisphosphonates

Clinical presentations

Osteomalacia may be asymptomatic and present radiologically as osteopenia. Clinically, patients with osteomalacia may present with diffuse bone pain and tenderness, fractures with little or no trauma (typically in the ribs, vertebrae and long bones) and proximal muscle weakness, which may be associated with a waddling gait.

History and physical examination should look for symptoms and signs of the possible underlying cause.

Children with rickets may present with hypotonia, growth retardation and skeletal deformities.

The laying down of uncalcified osteoid at the metaphases leads to widening of the ends of the long bones. This may be seen as ‘rachitic rosary’ in the ribs (enlarged ends of the ribs resembling beads at the costochondral junction) and at the level of the ankle and the wrist. Other skeletal deformities include frontal bossing, pectus carinatum and bowing of the long bones.