Fracture risk secondary to disease

This PhD dissertation was accepted by the Anatomical Institute, Aarhus University, and defended on October 31, 2003.

Official opponents: Kal J. Obrant, Sweden, and Anders Foldspang.

Correspondence to: Peter Vestergaard, The Osteoporosis Clinic, Aarhus Amtssygehus, Tage Hansens gade 2, DK-8000 Aarhus C, Denmark.
E-mail: p-vest@post4.tele.dk

Dan Med Bull 2004;51:154.

ABSTRACT

The PhD dissertation is based on 11 previously published original articles elaborated during my employment at the Osteoporosis Clinic, Aarhus Amtssygehus from 1997 to 2001.

The skeleton is among the largest organs in the body and may be affected by both external factors and diseases. Patients with various disorders were included as models for the skeletal effects of these disorders.

Lack of external loading of the skeleton leads to a loss of bone mineral. Two studies were carried out in patients who were immobilised either due to spinal cord injury or due to muscular dystrophy or spinal muscular atrophy. In patients with spinal cord injury, a doubling of fracture risk was seen three years after the injury. A similar but more gradual increase was seen in patients with muscular dystrophy and spinal muscular atrophy probably reflecting the more gradual loss of muscle function.

An increased tendency to sustain traumas may increase the fracture risk even among patients with normal bone biomechanical competence. Epilepsy may increase the risk of falls, and these patients had more fractures after the diagnosis. Almost the entire increase in fracture risk was linked to seizures.

Decreased absorption of calcium, increased levels of inflammatory cytokines, and treatment with corticosteroids may all harm the skeleton. The effect of these factors was investigated in patients with inflammatory bowel diseases. In Crohn's disease where all three factors are present, increased fracture risk was observed. Bowel surgery seemed to reduce the fracture risk perhaps due to removal of inflammatory tissue and a reduced need for corticosteroids. In ulcerative colitis where malabsorption is not present and lower doses of corticosteroids are used, no increase in fracture risk was seen.

Patients with anorexia nervosa are severely malnourished, and these patients experienced an increased fracture risk that persisted long after the diagnosis was made. Patients with bulimia nervosa and other eating disorders do not often lose weight and they had a smaller increase in fracture risk than patients with anorexia nervosa.

Thyroid hormones increase bone turnover. In patients with hyperthyroidism the fracture risk increased after the diagnosis was made. In hypothyroidism a temporary increase in fracture risk was seen the first two years after initiation of levothyroxine substitution.

An increased fracture risk was seen in Cushing's syndrome. Among patients with pituitary disorders an increased fracture risk was present in patients with prolactinomas and patients with growth hormone deficiency. A non-significant decrease in fracture risk was seen in patients with acromegaly perhaps indicating an anabolic effect of growth hormone.

PTH increases bone turnover. In primary hyperparathyroidism an increased fracture risk was observed up to ten years before the diagnosis was made and treatment started. The increased fracture risk decreased to normal levels after surgical treatment.