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We have known of the increased risk of prematurely reduced bone mineral density (BMD) in children and young adults with cystic fibrosis since Mischler’s work of 20 years ago1 which documented significant deficiency in 44% of 27 patients. Bone metabolism, however, remained until recently an under-researched area of cystic fibrosis care, perhaps because patients were not expected to live long enough for osteoporosis to become a clinical problem. The average age at death is now over 30 years. Today’s young children with cystic fibrosis are expected to live into middle age. Long term survival after lung transplantation is creating a cohort of patients who enter their new lives with a low bone mineral content which is then subjected to a further damaging assault by immunosuppressive therapy. The threat of osteoporosis with all its attendant complications is a problem for all involved in the care of patients with cystic fibrosis.
The paper by Haworth et al 2 in this issue of Thorax is an important contribution to our understanding of bone mineral status in adult patients with cystic fibrosis. It is the first to examine the extent of the problem in a large heterogeneous population. Previous studies of children, mixed age groups, and severely compromised adults have often been limited by small patient numbers. In the study by Haworthet al BMD was assessed in the distal forearm, lumbar spine, femoral neck, and total hip and 34% of 143 patients had a Z score of –2 or less at one or more skeletal sites, at least tripling their risk of fracture compared with a non-cystic fibrosis population of the same age and sex. These results give a clear message to those of us caring for adult patients with cystic fibrosis: dual energy x ray absorptiometry (DXA) must become a routine in the assessment of our patients (Haworthet al have shown that volumetric measurements are not necessary). This is perhaps another reason why all patients with cystic fibrosis should be assessed at least annually at a cystic fibrosis centre where the scanners are available. But what can we do to redress the problem in those with a low BMD and how can we prevent it in others?
Possibly because of the disparate populations studied, previous research serves only to confuse. Age, respiratory function data, disease severity, gonadal function, glucocorticoid use, and physical activity have all been suggested and refuted as predictors of decreased BMD. Haworth et al add further data to these arguments and, importantly, clarify
the picture by showing a clear relationship between BMD and disease severity (% predicted forced expiratory volume in one second (FEV1), body mass index (BMI), and levels of C reactive protein (CRP)) and physical activity, as well as a 38% prevalence of vitamin D insufficiency. They rightly state that correlation does not mean causation and comment on our ignorance of bone mineral accretion data in the present generation of children with cystic fibrosis. Nonetheless, they have a clear message for paediatricians—preservation of lung function, maintenance of normal growth, and encouragement of exercise are the only interventions we know of which may positively affect BMD status. Children who cough must receive added treatment. All units must have eradication programmes forPseudomonas aeruginosa acquisition. Frequent contact with the specialist dietician is essential. At least annual measurement of vitamin D levels should be routine with an immediate response to low levels. We used merely to react to respiratory exacerbations in our patients. Now we try to prevent them. We should similarly try to prevent the unacceptably high level of low BMD illustrated by Haworth et al. We need research directed at accurately assessing the accretion of bone mineral content in children with cystic fibrosis and the efficacy of appropriate intervention studies.
Haworth et al have further and clearly defined the problem of reduced BMD in adult patients. They have drawn attention to the need for prospective and longitudinal studies to define the role of corticosteroids and to better elucidate causal factors. They have not commented on treatment for established osteopenia. Several cystic fibrosis units are assessing the efficacy of bisphosphonates in small numbers of their own patients. We are in danger of yet more inconclusive, anecdotal results in the field of cystic fibrosis treatment. This most important area of long term cystic fibrosis care deserves a properly funded, multicentre, randomised, control trial.
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