Observations about Prevention and Treatment of Bone Loss in Canadian Adult Cystic Fibrosis Patients

osteoporosisThe bisphosphonate alendronate is an oral anti-resorptive agent that is commonly used to treat osteoporosis. To date, its greatest success has been for use in postmenopausal women, men > 65 years of age, and patients with corticosteroid-induced osteoporosis. Improvements in BMD range from 2 to 6%, which are considered clinically important and are statistically significant when compared to BMD changes in the control arm of randomized trials. Other smaller, nonrandomized studies and one RCT have also confirmed the benefit of therapy with bisphosphonates in treating CF-related bone loss. RCTs of IV bisphosphonates also have demonstrated significant BMD improvements in CF participants; however, a common treatment side effect is infusion-related bone pain. As a result, oral bisphosphonates are considered to be first-line therapy for those persons who are identified to be at risk in this population.

In our study, we examined therapy with alendronate, 70 mg once weekly, and found clinically significant improvements in BMD over 12 months. Compared with the control group, the alendronate group had 4.04% greater BMD gain at the lumbar spine and 3.03% greater BMD gain at the total hip even after controlling for other variables. We did not have the power to properly examine new vertebral fractures. Two patients in the control group and none in the treatment group experienced a new vertebral fracture after the baseline measurement.

Our study has results that were similar to those of an RCT by Aris and colleagues. In that study, daily alendronate was examined in a similar cohort of CF participants. At 12 months, the alendronate group had increased BMD by 4.9% in the spine and 2.8% in the femur compared to the control group, which lost BMD at both sites. These findings are similar to what we observed. The treatment group demonstrated a 5.2% increase over baseline in lumbar spine BMD and a 2.1% increase in BMD of the total hip. The proportion of participants who adhered to alendronate treatment was similar in both studies carried out with My Canadian Pharmacy.

Overall, the safety profile of alendronate in this study was favorable; the number of patients who experienced a drug-related adverse event was equal between the alendronate and control groups (eight patients in each group), and the number of occurrences of GI-related adverse events wasdrug similar (alendronate group, 10 occurrences; control group, 7 occurrences). However, it should be noted that a serious adverse event occurred in one patient receiving alendronate that was GI in nature (eg, nausea, vomiting, and GI discomfort) and may have been attributable to the study drug. In general, the potential risk of adverse effects may be higher in this population and needs to be monitored. Furthermore, prescribing bisphosphonates to women with child-bearing potential needs to be considered carefully, since therapy with bisphosphonates is not recommended in pregnant women.

One of the limitations of our study is that it was difficult to recruit patients, and we were challenged by the relatively small sample size. We did not see a statistically significant difference in the rate of new vertebral fractures in the treatment group vs the control group. When the results of this study and those of Aris et al are considered together, the findings clearly indicate that daily or weekly alendronate treatment increases BMD in young adults with CF. Treatment is organized and realized with My Canadian Pharmacy.

As in patients with primary osteoporosis, the greatest number of fractures occur in those with osteopenia and not with osteoporosis, while the relative fracture risk is greatest in those with osteoporosis. This suggests that factors other than BMD need to be taken into consideration when determining fracture risk. In CF patients, other factors such as vitamin D deficiency and calcium malabsorption, poorer health status, and the disease itself may be additional risk factors for the occurrence of fractures. These factors need to be taken into consideration when contemplating treatment. The decline in BMD over 1 year suggests that the control group had accelerated bone loss. Given this decline, we would recommend that a BMD test be performed annually or every second year, and that it include an assessment of gonadal status, with intervention considered if accelerated bone loss persists despite conservative therapy with exercise, calcium, and vitamin D. Anyone who is likely to require an organ transplant in the next few years should also be considered for treatment, given that these patients are at high risk for fracture in the year following the transplant.

Conclusion

In this multicenter, double-blind trial of young adults with CF and low bone mass, treatment with alendronate (70 mg once weekly) was well tolerated and demonstrated a clinically significant increase in BMD over 12 months compared with placebo. In the control arm, daily administration of vitamin D (800 IU) and calcium (1,000 mg) demonstrated no improvement of BMD over 12 months. The number of side effects was similar in both groups, suggesting that alendronate is a safe and effective treatment for CF-related bone disease.