Brief Summary

This is a two-year prospective, double-blind trial of two different doses of vitamin D supplementation in adults with neurofibromatosis type 1 (NF1) who are insufficient in serum 25-(OH) vitamin D [25(OH)D] at the time of enrollment. 

OBJECTIVE

Osteoporosis and vitamin D insufficiency are common manifestations of NF1, but there are no proven preventative or treatment strategies in NF1 patients. This study is designed to assess the efficacy of oral vitamin D therapy to prevent abnormal loss of bone mass in young adults with NF1.

HYPOTHESIS

We hypothesize that BMD in patients with NF1 and vitamin D insufficiency can be preserved by oral vitamin D and calcium supplementation.

SPECIFIC AIM

This is a randomized clinical trial of oral vitamin D therapy in adults with NF1 and vitamin D insufficiency, comparing the effects of a 600 IU daily supplement of cholecalciferol versus a therapeutic dose of cholecalciferol (4,000 IU/day) on maintenance of bone mineral density. All participants will also take an oral calcium supplement (400 mg elemental calcium) daily.

Inclusion Criteria

All individuals with NF1 (neurofibromatosis type 1), based on NIH diagnostic criteria, who are between the ages of 25 and 40 years, are potentially eligible for this study. Exclusion criteria will be reviewed prior to enrollment. All eligible participants will be enrolled in the study and then screened for serum 25(OH) vitamin D levels. Individuals with levels between 9 and 29ng/ml are eligible to receive vitamin D supplementation at one of 2 doses.

Exclusion Criteria

1)            diagnosis of Paget’s disease, hyperthyroidism, hyperparathyroidism, or other medical condition that affects bone health

2)            they foresee that they will be unable to comply with the two-year study protocol

3)            Pregnant, planning to conceive within the next two years, or is less than 6 months post-delivery or lactation.

4)            vitamin D supplementation in the last 3 months equal to or greater than 600IU per day

5)            oral or IV glucocorticoid use for over 3 months

6)            bisphosphonate therapy for more than 3 months

7)            calcitonin therapy for more than 3 months

8)            calcium supplementation in last 3 months equal to or greater than 1000mg per day

9)            malignant peripheral nerve sheath tumor (MPNST)

10)        history of kidney stones in last 5 years

11)        individuals with metal instrumentation in spine or hip that preclude accurate DXA interpretation.

12)        inability to obtain blood samples on routine venipuncture

13)        anti-epileptic medical therapy

14)        anticoagulant medical therapy