A 64-year-old woman with a history of well-controlled epilepsy, cardiac failure and depression presented with a three-month history of generalised aches and pains, which were present throughout the day. There was no morning stiffness.
She had had no seizures for about 10 years, but remained on regular and long-standing antiepileptic medication (phenytoin). Clinically, there was no evidence of cardiac failure.
A routine haematology and biochemistry screen revealed a moderately raised plasma viscosity, normal calcium, but a significantly raised alkaline phosphatase.
When the patient telephoned for the results of the blood tests, she explained that she could hardly walk now and had had a few falls. Her son drove her to the surgery and helped her in. It was obvious that she had a serious mobility problem.
A pelvic X-ray was arranged, querying a pelvic fracture (although there was no history of trauma). The result showed that there were radiological abnormalities consistent with osteomalacia, with no evidence of any fracture.
The patient was seen by the endocrinologists and started on vitamin D and calcium supplements, and she made a dramatic improvement. A few months later, when she returned for routine follow-up, she was walking normally.
Metabolic bone disease
Osteomalacia is classified as a metabolic bone disease. In children, before fusion of the epiphysis, deficiency of vitamin D may result in rickets.
In adults, vitamin D deficiency can result in low serum calcium and phosphate, which can lead to impaired mineralisation of the bone matrix, called osteoid. This is what we know as osteomalacia.
The amount of bone may be normal, but the bone matrix may be relatively less calcified. This poorly mineralised bone matrix has less strength compared with unaffected bone and hence is more prone to fracture.
If weight-bearing, the bone may buckle, although clinically apparent deformity is uncommon.
These changes can manifest as pain or tenderness and pathological fractures can occur. Myopathy can be present, leading to abnormal gait, but often, symptoms are vague.
It is not uncommon for biochemical abnormalities to be found before clinically apparent symptoms and signs present themselves.
Vitamin D deficiency
There are many causes of vitamin D deficiency, but common ones include poor exposure to sunlight (do not forget use of sunscreen) and lack of vitamin D in the diet, or a combination of both. These factors often put the older patient at greater risk of osteomalacia.
Other causes include malabsorption, chronic kidney disease and, as in this case, anticonvulsant therapy. Anticonvulsants can impair key steps in vitamin D metabolism, which in turn leaves less of the biologically active elements of vitamin D available.
Deficiency of vitamin D results in reduced gut absorption of calcium and this in turn stimulates the parathyroid glands to secrete more parathyroid hormone. This mobilises calcium from bones, which explains the rising alkaline phosphatase levels.
This secondary hyperparathyroidism leads to conservation of the urinary calcium loss, which also encourages urine phosphate loss. This can lead to low serum phosphate, which can have a negative effect on skeletal health.
Radiological examination may be normal but sometimes pseudofractures (Looser's zones) can be seen. It is thought these are caused by arterial pulsations abutting against the bone.
Once the diagnosis is made, usually on the basis of biochemical and radiological investigations, treatment is aimed at correcting metabolic abnormalities.
Vitamin D supplements and correcting the calcium and phosphate abnormalities are the basis of pharmacological interventions. The dose and form of medication will be determined by the cause and extent of the abnormalities.
Their impact can be monitored by checking alkaline phosphatase levels, calcium and renal function. Encourage sunlight exposure (bearing in mind the risk of skin cancer and sun damage) and give dietary advice, as well as written information about the condition and treatment.
- Dr Brown is a GP in Leeds
Arthritis Research UK. Osteomalacia. www.arthritisresearchuk.org/arthritis-information/conditions/osteomalacia.aspx.