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Pain Medicine 2012; 13: 735–736
Wiley Periodicals, Inc.
Hypovitaminosis D and Pain in Cystic Fibrosis
Reprint requests to: Luca Mascitelli, MD, Comando
Brigata alpina “Julia,” Medical Service, 8 Via S.
Agostino, Udine 33100, Italy. Tel: +390432584044;
Fax: +390432584053; E-mail: [email protected].
Conflict of Interest: WBG receives funding from the UV
Foundation (McLean, VA), the Sunlight Research Forum
(Veldhoven), Bio-Tech-Pharmacal (Fayetteville, AR), the
Vitamin D Council (San Luis Obispo, CA), and the
Vitamin D Society (Canada).
Drs. Mascitelli and Goldstein have no conflicts of interest
to disclose.
To the Editor,
Cystic fibrosis (CF) is the most common life-shortening
genetic disease in whites. It principally affects the lungs,
pancreas and gastrointestinal tract [1]. Advances in the
treatment have improved the life expectancy of people
with CF [2]. The increased longevity of adults with CF is
accompanied by a rising prevalence of secondary complications including pain [3], which can be associated with
the diagnosis and treatment of the disease, and the
disease itself [4].
A recent study [5] found that 82% of patients reported pain
within the past month, the most common sites being the
head, sinuses, back, and chest. Pain frequently interfered
with general activities (41.9%), mood (56.8%), and work
(47.3%). Symptoms of depression and anxiety, as well as
lower quality-of-life scores, were associated with the presence of pain. Furthermore, it was also found that pain
increased the risk of severe pulmonary exacerbations and
death [5].
Factors associated with pain in patients with CF are poorly
understood. We suggest that hypovitaminosis D may partially explain this association.
Decreased bone mineral density and increased risk of
fracture are common complications in CF. It has been
reported that 50–75% of adults with CF have low bone
density, with approximately 20–25% having osteoporosis
and 40% having osteopenia [6]. Multiple factors contribute
to this increased risk of osteoporosis and osteopenia, and,
among them, hypovitaminosis D represents an important
factor. Vitamin D insufficiency is significantly more prevalent among individuals with CF compared with healthy
control subjects, most likely secondary to low exposure to
sunlight, poor nutrition, and malabsorption of fat-soluble
vitamins resulting from pancreatic insufficiency [6].
On the other hand, it is well known that a clinical feature of
osteomalacia, a disorder of bone mineralization caused by
pme_1372
735..736
severe vitamin D deficiency, is generalized bone pain.
Indeed, severe vitamin deficiency is not asymptomatic,
and, before the clinical presentation of osteomalaciarelated bone pain, severe hypovitaminosis D results in a
syndrome of persistent, nonspecific musculoskeletal pain,
which has been well documented: up to 93% of patients
with persistent pain have been reported to have hypovitaminosis D [7].
Because vitamin D deficiency and decreased bone
density are important complications in individuals with CF,
consensus guidelines for optimizing CF bone health have,
therefore, been developed, recommending that individuals
with CF receive vitamin D supplementation to maintain
their 25-hydroxyvitamin D [25(OH)D] level ⱖ30 ng/mL [8].
However, this recommendation was based on the relationship between 25(OH)D and parathyroid hormone (PTH)
levels in individuals without CF. In fact, it has recently been
demonstrated in patients with CF that correction to
ⱖ35 ng/mL resulted in a greater likelihood of suppressing
PTH levels below those associated with increased bone
loss [6].
In addition to its action on bone, there is increasing evidence
of extraskeletal health benefits of vitamin D. 1,25Dihydroxyvitamin D, the biologically active form of vitamin D,
is involved in the regulation of immune responses. Interestingly, one hypothesis for the cause of chronic widespread
pain is the activation of inflammatory cytokine responses after
infection; cytokines having been shown to modulate pain
perception both peripherally and centrally [9].
Therefore, although the threshold for optimum vitamin D
status is known to be considerably higher than that
required to prevent osteomalacia, it is still important to
establish the risk of pain across a broader range of
25(OH)D concentrations. This may be particularly important for pain individuals with CF who are at high risk of
vitamin D deficiency. For these patients, also for the management of pain, we recommend close monitoring of
vitamin D status and adequate supplementation in order
to reach and maintain 25(OH)D levels ⱖ35 ng/mL.
LUCA MASCITELLI, MD
Comando Brigata Alpina “Julia,” Medical Service
Udine, Italy
MARK R. GOLDSTEIN, MD, FACP
NCH Healthcare Group
Naples, Florida, USA
WILLIAM B. GRANT, PhD
Sunlight, Nutrition, and Health Research Center
San Francisco, California, USA
735
Mascitelli et al.
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