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


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

In This Article


The InCHIANTI Study is a prospective population-based study of the factors that contribute to mobility decline in older Italian adults. The study sample (1,155 participants aged 65-102) was randomly selected using a multistage stratified sampling method from two towns in the Chianti geographic area of Italy (Greve in Chianti and Bagno a Ripoli, Tuscany, Italy). The details of the data collection and sampling procedures have been described elsewhere.[18] Baseline data was collected from September 1998 through March 2000. All participants gave written consent for study participation, and the ethical committee of the Italian National Research Council of Aging approved the study.

Of the 1,155 participants, 197 were excluded: 100 who did not have blood drawn, 50 who had blood drawn but did not have serum 25(OH)D values, and 47 who had 25(OH)D values but not provide complete pain information. Therefore, 958 participants (529 women and 429 men) were included in the final analysis.

At the baseline interview, participants were asked questions about back and lower extremity (hip, knee, and foot) pain. If participants reported back pain that had occurred quite often or almost every day during the previous year, they were asked to rate their pain using a numeric pain rating scale, which has been validated for use in older populations with varying cognitive statuses.[19] This scale, which was shown on a card, included numbers from 0 to 10, with 0 indicating no pain and 10 indicating the worst pain imaginable. For the measurement of lower extremity pain, participants who reported having hip, knee, or foot pain for at least 1 month during the previous year were also asked to rate their pain in the same manner. Upper extremity pain in was not examined in the analyses, because these questions were not included in the database.

Pain was categorized into four categories based on location and severity. Location was divided as back pain (thoracic to lumbar) or lower extremity pain (hip, knee, and foot). If the participant reported pain anywhere in the spine from the cervical to the lumbar region, they were considered to have back pain. If the participant reported pain in the hip, knee, or foot, they were considered to have lower extremity pain. Based on previous work, moderate pain severity (>3 on a scale of 0-10), which is thought to be a clinically important level of pain, was used as the break point.[18] Therefore, four pain categories were created: mild or no pain in the lower extremities or back; moderate to severe back pain, no lower extremity pain; moderate to severe lower extremity pain, no back pain; and lower extremity and back pain with moderate to severe intensity in at least one location.

Fasting blood samples were collected in the morning after a 12-hour fast, centrifuged, and stored at -80°C. Serum levels of 25(OH)D were measured using radioimmunoassay (RIA kit, DiaSorin, Stillwater, MN). The intra- and interassay coefficients of variation for vitamin D were 8.1% and 10.2%, respectively.

Covariates included specific variables thought to confound the association between serum 25(OH)D levels and pain, including age, body mass index (BMI), cognitive status, depressive symptoms, month of vitamin D assessment, calcium intake, and serum creatinine levels. BMI was calculated as weight in kg divided by height in m2. Cognitive status was measured according to Mini-Mental State Examination (MMSE) score. Depressive symptoms were examined using the Centers for Epidemiologic Studies Depression Scale (CES-D) score. Months of vitamin D assessment was included to account for seasonal variation in 25(OH)D levels (nmol/L), because greater sunlight exposure during spring and summer could increase measurement levels. Calcium intake (mg/d) was collected using the food-frequency questionnaire originally developed and validated for the assessment of dietary intake in Italian volunteers participating in the European Prospective Investigation into Cancer and Nutrition.[20] Serum creatinine (mg/dL; a marker of kidney function) was measured using a standard creatinine Jaffe method (Roche Diagnostics, Mannheim, Germany). Parathyroid hormone (PTH) levels were measured using a two-site immunoradiometric assay kit (N-tact PTHSP; DiaSorin). The intra- and interassay coefficients of variation for vitamin D were less than 3.0% and 5.5%, respectively.

Vitamin D deficiency was defined as 25(OH)D less than 25.0 nmol/L, consistent with definitions reported in the literature.[21] Descriptive analysis included reporting means±standard deviations for continuous variables and numbers and percentages for categorical variables according to gender and vitamin D category. Within-sex comparisons were made across vitamin D categories using t-tests for continuous variables and chi-square tests for categorical variables. The covariate-adjusted odds ratios were estimated using multinomial logistic regression in sex-stratified models.[22] This approach is appropriate for semi-ordinal outcomes, because it does not assume a linear association between vitamin D deficiency status and pain category. Using the group with no or mild lower extremity and back pain as the reference outcome category, the association between vitamin D deficiency status and each pain category was separately determined. All analyses were conducted using SAS version 8.02 (SAS Institute, Inc., Cary, NC).


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