Treatment of Cystic Fibrosis-Related Bone Disease

In a recently published article, authors outlined the non-pharmacologic and pharmacologic therapies for cystic fibrosis bone disease (CFBD) across various stages of life for people with cystic fibrosis (CF). UPMC Division of Endocrinology and Metabolism faculty Jagdeesh Ullal, MD, is the first and corresponding author. 

Due to the increasing longevity of people with CF, there is an increased interest in CFBD — a complex and multifactorial disease. CFBD results from hypomineralized bone that leads to poor strength, structure, and quality, increasing susceptibility to fractures. 

Physicians who treat patients with CFBD must tailor treatment to each patient with nuance based on available guidelines while simultaneously balancing therapeutic benefits to risks of long-term use. Bisphosphonates are the current mainstay treatment, but the long-term effects are not fully understood. 

Non-pharmacological Therapy

Minimizing Respiratory Exacerbations

CF pulmonary exacerbations are temporarily associated with elevated inflammatory markers, suggesting that acute inflammatory response increases bone resorption and diminishes bone formation. 

Nutrition

Numerous studies show an association between poor nutrition and low area bone mineral density in CF. Nutrition guidelines for optimized pulmonary function may also optimize bone health. 

Glucocorticoids

While glucocorticoids are a common treatment for CF pulmonary exacerbations, they have a negative impact on bone health. Avoidance of this therapy or the use of the lowest dose when necessary is likely to preserve bone mineral density. 

CF Related Diabetes

All forms of diabetes impact bone health, but people with CF are particularly vulnerable to the effects hyperglycemia has on bone density. 

Physical Activity

Exercise is associated with higher bone mineral density amount of the general population and a study found the same results for adults with CF. 

Calcium, Vitamin D, and Vitamin K

Adequate calcium intake is necessary during childhood and adolescence for the general population, but in CF there are multiple factors leading to calcium deficiency. This includes malabsorption, increased intestinal permeability, increased urinary calcium excretion, vitamin D deficiency, and changes in diet. 

Vitamin D deficiency can cause secondary hyperparathyroidism leading to adverse bone density and strength, while overtreatment of vitamin D deficiency can suppress PTH and reduce health bone turnover. Annual assessment is necessary after dose changes.

Vitamin K is necessary for clotting factor production and the carboxylation of osteocalcin into its active form. There is also limited evidence that supports vitamin K supplements can improve bone mineralization. 

Secondary Causes

Even for CF patients, the evaluation of secondary causes of bone loss should be considered such as celiac disease, thyroid dysfunction, and hypogonadism.

Pharmacologic Therapy

Since CFBD is a multifactorial disease, pharmacotherapy should be considered in conjunction with non-pharmacologic therapy. 

Antiresorptive Therapy

Biophosphonates are used in the treatment of osteoporosis and low-trauma fractures resulting in a net increase in bone mineral content and bone mineral density. 

Denosumab – a monoclonal antibody directed against the receptor activator of RANKL that stimulates osteoclast action breaking down bone – has theoretical evidence showing it could be beneficial in CFBD.

Selective estrogen receptor modulators Raloxifene and Bazedoxifene are approved for prevention of postmenopausal osteoporosis. 

Calcitonin is a nasal spray for the treatment of postmenopausal osteoporosis when alternative treatments are not feasible or suitable. 

Anabolic Therapy

There are three anabolic bone agents — a group of medications that promote new bone formation — that are currently FDA approved for treatment of osteoporosis: Teriparatide, Abaloparatide, and Romozosumab. 

CFBD in Lung Transplant

Initiation of pharmacologic therapy should be considered before transplant due to significant bone loss after transplant. The bone loss occurs because of steroid administration for immunosuppression or prolonged immobilization. 

CFTR Modulators

About 90% of CF patients can be treated with a highly effective CFTR modulator — a revolutionary class of medications that target the underlying genetic defect that causes CF. CFTR modulators might improve bone density by targeting dysfunctional CFTR in the bone or improving other risk factors for CFBD. 

Learn more about the set of guidelines by reading the full article here.

Reference

Ullal J, Kutney K, Williams KM, Weber DR. Treatment of cystic fibrosis related bone disease. J Clin Transl Endocrinol. 2021;27:100291. Published 2021 Dec 21. doi:10.1016/j.jcte.2021.100291