Screen for vitamin-D deficiency in all patients with persistent, nonspecific musculoskeletal pain

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Dec 16, 2003

Screen for vitamin-D deficiency in all patients with persistent, nonspecific

musculoskeletal pain

Rochester, MN - Screening all patients presenting with persistent,

nonspecific musculoskeletal pain for vitamin-D deficiency should be a

standard practice in clinical care, say US researchers, writing in the

December 2003 issue of the Mayo Clinic Proceedings [1]. They report on a

study carried out at an inner-city primary-care clinic affiliated with the

University of Minnesota, in which 93% of outpatients presenting with such

pain were found to be vitamin-D deficient, many severely so. Five patients

had undetectable levels of vitamin D, and all of the patients under 30 years

of age (n=33) were deficient.

" These findings are remarkably different from what is taught at medical

school. We would expect vitamin-D deficiency in old persons or the

housebound, " says lead researcher Dr Greg Plotnikoff (University of

Minnesota, Minneapolis; currently at Keio University, Tokyo, Japan). " We

found the worst vitamin-D deficiency in young personsespecially women of

childbearing age. We were stunned to find no vitamin D at all in 5 patients

who had been told their pain was 'all in their head.' "

All of the patients were at risk of misdiagnosis and suboptimal treatment of

their pain condition, the researchers note. Severe deficiency of vitamin D

is not asymptomatic, they comment: it results in a syndrome of persistent,

nonspecific musculoskeletal pain, even before the clinical manifestation of

osteomalacia bone pain.

Inadequate mineralization of bone

Vitamin-D deficiency causes muscle weakness and muscle aches and pains in

both adults and children, comments Dr Holick (Boston University

School of Medicine, MA) in an accompanying editorial [2]. The lack of

vitamin D leads, via parathyroid hormone and calcium, to inadequate

mineralization of the bone, so that the collagen matrix becomes rubbery, and

in hydrating and expanding it exerts an outward pressure on sensory nerves.

" This is the likely explanation of why patients with osteomalacia often

experience a dull, unrelenting aching sensation in their bones, " Holick

says, but he points out that " these symptoms are either dismissed or

misdiagnosed as fibromyalgia by many physicians. "

" A physical examination that includes application of minimal pressure with

the thumb or forefinger on the sternum, anterior tibia, or radius and ulna

often will elicit pain and discomfort, which is a helpful diagnostic sign

for osteomalacia, " he adds.

Vitamin-D deficiency has again become a major health problem

Plotnikoff et al's finding of vitamin D deficiency is " newsworthy " but is

not unexpected, Holick comments in the editorial, citing several other

recent studies that have found vitamin-D deficiency in US populations. " It

is inconceivable with all the advances in modern medicine that vitamin-D

deficiency should be a health concern in the US, " he writes. Most physicians

assume that vitamin-D deficiency, which plagued children in the 17th through

19th centuries, has been eradicated, but it has again become a major health

problem for all ages and races.

" All physicians should be alert to vitamin-D deficiency. "

There are a multitude of reasons for this, he comments. Extremely few foods

naturally contain vitamin D, and fortification of foodstuffs with the

vitamin was abandoned after an outbreak of vitamin-D intoxication during the

1950s (in a limited number of children in the UK). Most vitamin D (90% or

more) comes from exposure to sunlight, but this has been discouraged in

recent years by health-education messages aimed at preventing skin cancer.

Some of these advise avoiding all direct exposure to the sun and always

using a sunscreen when outdoors, but a sun protection factor of 8 reduces

the capacity of the skin to produce vitamin D by 95%, Holick points out.

All physicians should be alert to vitamin-D deficiency, Holick says.

Patients should have their vitamin-D status tested once a year, preferably

at the end of the fall season, to ensure that they do not become vitamin-D

deficient before winter.

Study finds severe deficiency of vitamin D

Plotnikoff et al investigated 150 patients (ranging from 10 to 65 years old)

who presented with persistent, nonspecific musculoskeletal pain. None of

these patients had fibromyalgia, temporomandibular disorder, or complex

regional pain syndrome, and none had any known medical condition that would

interfere with the production or absorption of vitamin D, they note.

They measured serum levels of 25-hydroxyvitamin D, a standard marker for

vitamin-D status. As there is no universal consensus about what level

constitutes vitamin-D deficiency, the researchers used a physiological

definition of 20 ng/mL (50 nmol/L) or lessbelow this, serum levels of

parathyroid hormone (PTH) increase, and even slight increases in serum PTH

result in increased bone turnover and accelerated bone loss.

Overall, 140 of 150 patients (93%) were found to have deficient levels of

vitamin D, regardless of immigrant status, sex, race, or season. Mean serum

levels of 25-hydroxyvitamin D were 12.08 ng/mL, which is in the moderately

severe to moderately deficient range, the researchers comment.

Previous studies have identified vitamin-D deficiency in immigrant

populations, they note. In their own study, just over half of the patients

were from immigrant populations. Among these, vitamin-D deficiency was found

in all (100%) of the East African (n=34) and Hispanic (n=5) individuals and

in 89% (39/44) of Southeastern Asians. The researchers comment that,

unexpectedly, they also found vitamin-D deficiency in all of the African

American (n=22) and American Indian (n=10) individuals and in 83% (29/35) of

white patients.

The degree of severity of vitamin-D deficiency was inversely

disproportionate by age groups. All of the younger patients (6 of whom were

aged 10 to 19, 27 aged 20 to 29) were deficient and had significantly lower

levels of serum 25-hydroxyvitamin D (mean 9.18 ng/mL) than those aged 50 or

more (mean 13.3 ng/mL). These young adults are at high risk of failure to

develop optimal peak bone mass, the researchers comment. Women of

childbearing age had significantly lower levels (mean 9.56 ng/mL) than older

women (14.09 ng/mL), and the level of deficiency found in these younger

women puts them at risk of bearing children with adverse fetal effects or

severe neonatal illness. Nearly half of these younger women were severely or

profoundly vitamin-D deficient, they note. Men were equally deficient (mean

11.72 ng/mL), even though they accounted for only 29% (44/150) of the study

participants.

Of the 5 patients who had undetectable levels of 25-hydroxyvitamin D, 4 were

under 35 years of age and 3 were nonimmigrants (1 was a white 23-year-old

female, 2 were African American). All of these patients had had extensive

contact with the healthcare system and had been variously diagnosed with

dysthymia, joint disease, stress reaction, and/or major depressive disorder;

all were taking nonsteroidal anti-inflammatory drugs (NSAIDs), and 2 were

also on antidepressants. In none of these patients was osteomalacia

suspected.

" The presence of nearly universal hypovitaminosis D in Minnesota cannot be

ruled out. "

Discussing the limitations of their study, Plotnikoff et al point out that

they took only 1 measurement and investigated only patients with nonspecific

musculoskeletal painthey did not have matched controls in the general

population. They also note that the level of vitamin D found in their study

is much lower than those reported in other studies, even in 1 study that

looked specifically at patients with painful conditions (fibromyalgia and

systemic lupus erythematosus) and was conducted at a geographically similar

latitude (and hence similar sunshine levels). Nevertheless, the findings may

reflect the background prevalence of hypovitaminosis D, and the presence of

nearly universal hypovitaminosis D in Minnesota cannot be ruled out, the

researchers caution.

Screen all patients with musculoskeletal pain

" These results support screening of all outpatients with persistent,

nonspecific musculoskeletal pain for hypovitaminosis D. These patients are

at high risk for the consequences of unrecognized and untreated

hypovitaminosis D, " say Plotnikoff et al. The findings of this study show

that those at risk include populations who have, until now, been considered

low risk, including nonelderly, nonhousebound, and nonimmigrant patients of

either sex. Nonimmigrant women of childbearing age may be at particularly

high risk, they add.

" Vitamin D deficiency has again become a major health problem for all ages

and races. "

" Because osteomalacia is a known cause of persistent, nonspecific

musculoskeletal pain, screening all outpatients with such pain for

hypovitaminosis D should be standard practice in clinical care, " the

researchers conclude.

" A prospective US trial to assess management of persistent, nonspecific pain

by prescription vitamin-D replenishment is urgently needed, " they add.

Take-home message: measure vitamin D

" The take-home message from Plotnikoff and Quigley's observations is that

when patients with nonspecific skeletomuscular pain are evaluated, their

serum 25-hydroxyvitamin D levels should be obtained, " says Holick in the

editorial. " Physicians should discard the laboratory-reported lower limit of

the normal range. A serum 25-hydroxyvitamin D level of at least 20 ng/mL is

necessary to minimally satisfy the body's vitamin-D requirement. Maintenance

of a serum level of 25-hydroxyvitamin D of 30 to 50 ng/mL is preferred. "

Zosia Chustecka

Sources

1. Plotnikoff GA, Quigley JM. Prevalence of severe hypovitaminosis D in

patients with persistent, nonspecific musculoskeletal pain. Mayo Clin Proc

2003 Dec; 78(12):1463-70.

2. Holick MF. Vitamin D deficiency: what a pain it is. Mayo Clin Proc 2003

Dec; 78(12):1457-9.