Associations Between Vitamin D Status and Pain in Older Adults: The Invecchiare in Chianti Study

Gregory E. Hicks, PhD, PT; Michelle Shardell, PhD; Ram R. Miller, MDCM, MSc; Stefania Bandinelli, MD; Jack Guralnik, MD, PhD; Antonio Cherubini, MD; Fulvio Lauretani, MD; Luigi Ferrucci, MD, PhD

Disclosures

J Am Geriatr Soc. 2008;56(5):785-791. 

In This Article

Discussion

The initial hypothesis was that lower levels of 25(OH)D would be associated with the presence of significant pain in older adults; the significant relationship between vitamin D status and moderate to severe back pain in older women but not men partially supported this hypothesis. According to the data, vitamin D deficiency was not associated with higher levels of lower extremity pain or dual-region pain; furthermore, non-deficient vitamin D status was not associated with lower levels of pain, although a unique relationship was found between vitamin D status and back pain, in that older women with vitamin D deficiency were more likely to have significant back pain. It is not completely clear why this specific relationship between back pain and vitamin D exists in this cohort. One plausible explanation is that vitamin D deficiency leads to osteomalacia, which commonly presents as chronic low back pain clinically and is more commonly seen in women.[23] This may explain why the findings demonstrate this significant relationship between vitamin D status and back pain in older women. Similar to these findings, other studies have shown a relationship between back pain and vitamin D status, but none have shown a relationship between vitamin D and pain in other body regions.

In terms of sex differences, in general, older women appeared to bear a higher burden of vitamin D deficiency and pain, particularly having pain in more than one location. The findings regarding pain are consistent with other reports in the literature.[2,17] Thus, it may be even more important to examine underlying causes of pain in older women, particularly the role of vitamin D status in back pain.

Public health awareness of the need for adequate vitamin D levels is steadily increasing in Europe and North America because of emerging evidence that vitamin D deficiency can lead to a host of poor health consequences, including greater fracture risk, functional decline, and pain.[4,5,6,8,9] Due to multiple factors, vitamin D deficiency is common in older adults.[24,25] With limited sources of vitamin D available in nature (primarily fatty fish), dietary intake is not a reliable source for vitamin D acquisition.[26] Thus, the consumption of vitamin D-fortified foods and sunlight exposure and the resultant synthesis in the skin are the primary mechanisms by which vitamin D is acquired.[27] In older adults, this is problematic because of the limited sunlight exposure, especially in the homebound, the reduced capacity of older skin to synthesize vitamin D, and the greater prevalence of nutritional deficiencies in general and intolerance to dairy products in particular in this age group.[27] In addition to the aging subgroup, people with darker skin pigmentation are also at greater risk because of a need for longer exposure periods for maximal absorption of ultraviolet rays.[28] Living at higher latitudes also adds to the deficiency problem because of the shorter periods of available ultraviolet light.[28] Thus, special consideration should be given to screening people in these at-risk populations to prevent vitamin D deficiency and its negative sequelae.

Although the relationship between vitamin D status and pain has been examined in smaller studies, to the authors' knowledge, this is the first large-scale population based study to examine this issue in older adults. A small case series described an unusual pain syndrome that failed to respond to traditional pain management strategies but was alleviated with the administration of a man-made form of vitamin D, ergocalciferol.[7] Another study also demonstrated an association between vitamin D deficiency and persistent, nonspecific musculoskeletal pain in a nonelderly sample of 150 patients.[9] They found that 93% of the sample would be considered vitamin D deficient and had never been tested for vitamin D status. The large prevalence of low vitamin D levels in this cohort may be a function of the study location (Minneapolis, MN), where people are unlikely to get enough sunlight exposure.[9] An investigation of the contribution of vitamin D deficiency to chronic low back pain (CLBP) status in a cohort of 360 patients (90% women) found that 83% of all patients had serum 25(OH)D levels less than 22.5 nmol/L and that there was a significant reduction in symptoms after vitamin D supplementation in those who were deficient.[6] In Saudi women, vitamin D deficiency is thought to be a serious problem due to limited sunlight exposure as a result of the intense heat and the avoidance of body exposure encouraged in Muslim communities.[6] Although all of these studies suggest a reduction in symptoms related to vitamin D supplementation, none of these studies was conducted as a randomized or placebo-controlled trial. Randomized trials examining various forms of vitamin D supplementation need to be performed before advocating its use for back pain.

In contrast to the studies demonstrating a positive relationship between vitamin D status and pain, there are also several studies that have found no relationship. For example, one found that vitamin D levels were not correlated with back pain as measured using a visual analog scale in women of various ages with osteoporosis,[14] although when comparing pain as measured using the Quality of Life Questionnaire of the European Foundation for Osteoporosis in those with those with deficient vitamin D status (<25 nmol/L) and those with sufficient status (25-50 nmol/L), it was found that the effect size was clinically relevant at 0.58 and was borderline significant (P = .05). In addition, there have been several studies that have evaluated pain as a secondary outcome when plain vitamin D was used as a supplement.[15,16,29] These studies have found that plain vitamin D is not sufficient to ameliorate back pain,[15,16,29] although use of a vitamin D-hormone analog, alfacalcidol, significantly reduced back pain severity in postmenopausal women with osteoporosis. All of these vitamin D studies (positive and negative), along with the findings of the current study, provide motivation for future work to understand the role of vitamin D in back pain and to evaluate the use of vitamin D analogs as potential treatments for pain.

Although the development of these vitamin D-related pain syndromes are not well understood, they are thought to be due to the development of osteomalacia, which is a condition characterized by softening of the bones, with resultant weakness, and bone fragility, caused by inadequate deposition of calcium or vitamin D.[11] Osteomalacia often presents itself as nonspecific musculoskeletal pain, particularly in the lumbar spine region, and is more commonly seen in women.[23] The mechanism by which vitamin D deficiency leads to pain has been proposed previously.[8,11] It is proposed that vitamin D deficiency causes a reduction in calcium absorption and thereby greater production of parathyroid hormone (PTH) to maintain blood calcium levels. Then PTH increases urinary excretion of phosphorus, leading to hypophosphatemia. Without sufficient calcium phosphate product levels in the circulation, the collagen matrix on the endosteal and periosteal surfaces of bones cannot be properly mineralized. Thus, when the improperly supported collagen matrix hydrates and swells, it causes pressure on the sensory-innervated periosteum, resulting in pain.[8,11] There is also evidence that vitamin D deficiency may lead to a faster rate of progression of osteoarthritis, the most common musculoskeletal disease in older adults.[30] This association, which may be mediated, in part, through an effect of vitamin D on bone mineral density, could also result in greater prevalence of pain in and around the joints, including those of the axial skeleton.[4,31]

Although the prevalence of back pain is similar between men and women, the association between 25(OH)D levels and pain were not the same in both sexes. This finding suggests a potential sex difference in the mechanisms underlying back pain in older adults. In the same way that women are more prone to bone loss over time (osteoporotic changes), it is logical that women would be more vulnerable to vitamin D-related pain because osteomalacia is on the pathway to osteoporosis. In terms of typical structural adaptations seen in aging bone, men and women exhibit greater total cross-sectional area (CSA) and medullary area over time, but women have a much smaller increase in CSA and a larger increase in medullary area.[32,33] As a result, women display a greater thinning of cortical area and thickness, resulting in a greater load per unit area (stress) being imposed on women's bones than in men. This greater stress leads to a greater likelihood of structural damage to the bone.[32,33] In addition, the greater cortical thinning seen in women may also make the bone more susceptible to the influences of low vitamin D status.[32,33] Given the small proportion of men in the sample who were vitamin D deficient, it is also possible that a true association between vitamin D status and pain is being masked because of sample size. In any event, the sex difference seen in the relationship between vitamin D and pain needs to be explored further.

A primary advantage of this study is the use of a large population-based sample with plasma 25(OH)D levels, which is the best clinical indicator of vitamin D body stores. It is important to highlight possible intervention points on the pathway to disability by identifying factors, such as vitamin D status and pain, that may lead to functional decline. The cross-sectional nature of the data does not allow temporality of vitamin D and pain categories to be determined; therefore, the observed association may be due to a noncausal relationship (e.g., unmeasured causal agents that may affect both vitamin D levels and pain). Although it is biologically plausible that vitamin D deficiency caused significant back pain, it is also possible that the women with significant back pain were more likely to stay indoors and self-limit their activities, leading to less sunlight exposure and thus to vitamin D deficiency. It is also not known whether the results of this study are generalizable to groups other than older Italians. With regard to the sex difference, one must consider that men are more likely to underreport pain, which may have affected the overall findings of the study. Although the sample size was sufficiently large to demonstrate the association between vitamin D status and back pain in women, it may not be large enough to show the associations with other pain groupings, especially in men, who are more likely to underreport pain. Finally, because the vitamin D-deficient participants in this study had poorer cognition, there may be some concern that their ability to understand the use of the numeric pain rating scale (NPRS) was compromised. It is likely that this is not the case, given the established concurrent validity for use of the NPRS in older adults with and without cognitive impairment,[19] as well as the evidence that 92% of nursing home residents with mild cognitive impairment (MMSE score 18-23) can complete the NPRS.[34]

In conclusion, low vitamin D status was associated with significant back pain in older women but not men. Given that low vitamin D status is fairly prevalent in older adults and that there are significant functional consequences to untreated chronic pain,[2] these findings argue strongly for querying older adults about their pain and potentially screening older women with significant back pain for vitamin D deficiency. Prevention of vitamin D deficiency in older women may be beneficial in reducing back pain severity and its deleterious functional consequences, but randomized, controlled trials will be needed before practice guidelines can be changed. Recent work in the area of vitamin D status and pain suggest a need for continued research in this area, particularly in older women and ethnic populations with darker skin who require greater levels of sunlight exposure to synthesize vitamin D.


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