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Eczema is associated with osteoporosis and fractures in adults: A US population-based study

2014; Elsevier BV; Volume: 135; Issue: 4 Linguagem: Inglês

10.1016/j.jaci.2014.10.043

1097-6825

Nitin Garg, Jonathan I. Silverberg,

Contact Dermatitis and Allergies

Patients with eczema have multiple potential risk factors for decreased bone mineral density (BMD), including using large quantities of topical corticosteroids, systemic corticosteroids, and chronic inflammation. Furthermore, eczema is associated with distraction from itch, mental health comorbidities, and sleep disturbance,1Silverberg J. Garg N. Paller A. Fishbein A. Zee P. Sleep disturbances in adults with eczema are associated with impaired overall health: a US population-based study.J Invest Dermatol. August 31, 2014; ([Epub ahead of print])https://doi.org/10.1038/jid.2014.325Abstract Full Text Full Text PDF Scopus (260) Google Scholar all of which predispose to fractures and other injuries.2Garg N. Silverberg J.I. Association between eczema and increased fractures, bone or joint injury in adults: a US population-based study.JAMA Dermatol. October 29, 2014; ([Epub ahead of print])https://doi.org/10.1001/jamadermatol.2014.2098Crossref Scopus (46) Google Scholar, 3Garg N. Silverberg J.I. Association between childhood allergic disease, psychological comorbidity, and injury requiring medical attention.Ann Allergy Asthma Immunol. 2014; 112: 525-532Abstract Full Text Full Text PDF PubMed Scopus (97) Google Scholar However, previous studies examining BMD in adults with eczema found conflicting results4Haeck I.M. Hamdy N.A. Timmer-de Mik L. Lentjes E.G. Verhaar H.J. Knol M.J. et al.Low bone mineral density in adult patients with moderate to severe atopic dermatitis.Br J Dermatol. 2009; 161: 1248-1254Crossref PubMed Scopus (33) Google Scholar, 5Aalto-Korte K. Turpeinen M. Bone mineral density in patients with atopic dermatitis.Br J Dermatol. 1997; 136: 172-175Crossref PubMed Scopus (29) Google Scholar, 6van Velsen S.G. Haeck I.M. Knol M.J. Lam M.G. Bruijnzeel-Koomen C.A. Two-year assessment of effect of topical corticosteroids on bone mineral density in adults with moderate to severe atopic dermatitis.J Am Acad Dermatol. 2012; 66: 691-693Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar and their risk of fractures has not been fully explored. In the present study, we analyzed data from a large-scale US-population–based study to assess the burden of fractures in adult eczema. We used the 2005-2006 National Health and Nutrition Examination Survey. Household surveys were performed in-person in English and Spanish, as well as health examinations, blood collection, and dual-energy x-ray absorptiometry (DEXA) in mobile examination centers. Survey results were weighted to represent the population of US adults using data from the US Census Bureau. Approval by the Northwestern University institutional review board was waived. Sociodemographic characteristics included age, sex, race, education level, and household income. Lifetime history of doctor-diagnosed osteoporosis and prednisone/cortisone use daily for at least 30 days were assessed. Daily tobacco and alcohol consumption habits were assessed. History of eczema was assessed by a positive response to the question, “Has a doctor or other health professional ever told (you/sample person) that (you have/sample person has) eczema?” To improve the specificity of self-reported eczema, subjects who reported a health care provider diagnosis of psoriasis were excluded from analyses. History of fractures was determined by asking “Has a doctor ever told (you/sample person) that (you/s/he) had broken or fractured … (your/his/her) hip?”, “… (your/his/her) spine?”, “… (your/his/her) wrist?”, “… any other bone after (you were/s/he was) 20 years of age?” A composite binary variable was created on the basis of the above responses. The BMD (g/cm2) of the hip and spine was measured by using DEXA on all eligible participants. Total femur, femoral neck, trochanter, and spine scans were performed with a Hologic QDR-4500A fan-beam densitometer (Hologic, Inc, Bedford, Mass) as previously described.7National Center for Health Statistics. National Health and Nutrition Examination Survey (NHANES) body composition procedures manual. Centers for Disease Control and Prevention, Hyattsville, MD2006Google Scholar BMD-for-age, sex, and race/ethnicity t scores were also determined on the basis of National Health and Nutrition Examination Survey reference standards.8Looker A.C. Borrud L.G. Hughes J.P. Fan B. Shepherd J.A. Melton III, L.J. Lumbar spine and proximal femur bone mineral density, bone mineral content, and bone area: United States, 2005-2008.Vital Health Stat 11. 2012; : 1-132Google Scholar Physical examination was performed,9Carroll M.D. National Center for Health Statistics (U.S.), Hispanic Health and Nutrition Examination Survey (U.S.)Serum lipids and lipoproteins of Hispanics, 1982-1984. U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control, National Center for Health Statistics, Hyattsville, MD1990Google Scholar body mass index was calculated, and blood samples were collected. Bivariate and multivariate analyses were performed with SURVEY procedures in SAS (version 9.4; SAS Institute, Cary, NC). Bivariate associations between eczema, fracture, metabolic factors, and sociodemographic variables were tested via logistic regression models. Bivariate associations between eczema and BMD were tested via linear regression models. Complete data analysis was performed. Two-way interaction terms between eczema and age, sex, race, and household income were tested. Interactions were included in final models if P was less than .01 and modification of estimates was more than 20%. A 2-sided P value of less than .05 was taken to indicate statistical significance. A total of 4972 people aged 20 to 85 years were included in this analysis. The prevalence (95% CI) of eczema was 7.4% (6.5% to 8.3%), of which 24.7% (18.8% to 30.5%) also had a lifetime history of asthma. The prevalence of any fracture was 32.3% (30.7% to 33.9%). Hip or spine fractures were described in 3.9% (3.3% to 4.6%), whereas 30.6% (29.0% to 32.2%) reported having “other” fractures. Associations with the prevalence of eczema and fractures are presented in Table E1 in this article's Online Repository at www.jacionline.org. Adult eczema was not associated with 25-OH vitamin D, calcium, parathyroid hormone, alkaline phosphatase, albumin, lactate dehydrogenase, C-reactive protein, or peripheral white blood cell counts compared with those without AD (see Table E2 in this article's Online Repository at www.jacionline.org). In multivariate models, eczema was associated with a significantly lower BMD t score for the total femur, including trochanter and total lumbar spine, but not femoral neck (Table I). In particular, eczema was associated with osteopenia (−2.5 < t score ≤ −1) and osteoporosis (t score ≤ −2.5) of the trochanter, but not of the total femur, femoral neck, or total spine (Table II). Adults with eczema had higher odds of any fracture, including hip/spine and other fracture. However, osteoporosis was self-reported in only 16.3% and 10.7% of the adults with eczema and a t score of −2.5 or less at the femoral neck or any site, respectively. In multivariate models, osteoporosis was associated with ever using oral corticosteroids daily for a month or longer (adjusted odds ratio [95% CI], 1.44 [1.05-1.99]; P = .02) but not associated with lifetime or 1-year history of asthma, peripheral eosinophil counts of more than 1000 cells/uL, or IgE level of more than 100 kU/L (data not shown).Table IAssociation between eczema and lower BMD t score in adults (n = 3377)EczemaBMD t score (95% CI)β (95% CI)P valueAdjusted β (95% CI)P valueTotal femur No0.04 (−0.01 to 0.10)0.00 (ref)—0.00 (ref)— Yes−0.25 (−0.44 to −0.06)−0.29 (−0.49 to −0.10).004−0.27 (−0.46 to −0.08).006Trochanter No−1.95 (−1.99 to 1.90)0.00 (ref)—0.00 (ref)— Yes−2.21 (−2.37 to −2.04)−0.26 (−0.43 to −0.09).003−0.25 (−0.42 to −0.08).004Femoral neck No−1.09 (−1.14 to −1.04)0.00 (ref)—0.00 (ref)— Yes−1.27 (−1.45 to −1.09)−0.18 (−0.37 to 0.01).07−0.13 (−0.31 to 0.04).14Total lumbar spine No0.58 (0.53 to 0.63)0.00 (ref)—0.00 (ref)— Yes0.40 (0.21 to 0.58)−0.18 (−0.37 to 0.01).06−0.22 (−0.41 to −0.03).02Boldface indicates statistical significance (P < .05). Open table in a new tab Table IIAssociation between eczema, osteopenia, osteoporosis, and fractures in adults (n = 4936)VariableNo eczemaEczemaFrequencyPercent (95% CI)FrequencyPercent (95% CI)OR (95% CI)P valueaOR (95% CI)P valueOsteopenia (−2.5 < t ≤ −1) Total femur58618.8 (17.2-20.5)4322.7 (16.1-29.2)1.31 (0.88-1.93).181.33 (0.85-2.07).21 Femoral neck130241.6 (39.6-43.7)8541.1 (33.5-48.7)1.06 (0.75-1.51).731.07 (0.74-1.55).74 Trochanter153447.8 (45.7-49.9)11154.7 (47.0-62.4)2.03 (1.24-3.33).0052.08 (1.27-3.42).004 Total spine2788.3 (7.1-9.4)1910.4 (5.3-15.5)1.29 (0.73-2.28).391.32 (0.74-2.36).34Osteoporosis (t ≤ −2.5) Total femur1012.6 (2.1-3.2)114.9 (1.6-8.3)2.04 (0.96-4.34).072.09 (0.93-4.70).08 Femoral neck40012.4 (11.1-13.8)3216.2 (10.4-21.9)1.40 (0.88-2.25).161.42 (0.85-2.39).19 Trochanter101532.4 (30.4-34.4)6734.1 (26.8-41.5)1.86 (1.10-3.15).021.97 (1.14-3.41).02 Total spine200.6 (0.3-0.9)20.8 (0-2.0)1.35 (0.29-6.3).711.23 (0.24-6.26).80Fracture Any fracture132731.60 (29.93-33.27)11840.77 (34.22-47.32)1.49 (1.12-1.96).0051.48 (1.10-1.99).01 Hip or spine fracture1753.70 (3.05-4.36)176.47 (3.10-9.84)1.80 (1.00-3.24).0471.87 (1.02-3.43).04 Other fracture124429.98 (28.33-31.63)11137.80 (31.36-44.25)1.42 (1.07-1.89).0161.40 (1.04-1.88).03aOR, Adjusted odds ratio; OR, odds ratio.Boldface indicates statistical significance (P < .05). Open table in a new tab Boldface indicates statistical significance (P < .05). aOR, Adjusted odds ratio; OR, odds ratio. Boldface indicates statistical significance (P < .05). The results of this study confirm and expand on previous studies that found a higher risk of fractures and other injuries among patients with eczema.2Garg N. Silverberg J.I. Association between eczema and increased fractures, bone or joint injury in adults: a US population-based study.JAMA Dermatol. October 29, 2014; ([Epub ahead of print])https://doi.org/10.1001/jamadermatol.2014.2098Crossref Scopus (46) Google Scholar, 3Garg N. Silverberg J.I. Association between childhood allergic disease, psychological comorbidity, and injury requiring medical attention.Ann Allergy Asthma Immunol. 2014; 112: 525-532Abstract Full Text Full Text PDF PubMed Scopus (97) Google Scholar Other studies of BMD in adults with AD/eczema found conflicting results. One found lower lumbar spine BMD only in patients using moderate to high potency topical corticosteroids,5Aalto-Korte K. Turpeinen M. Bone mineral density in patients with atopic dermatitis.Br J Dermatol. 1997; 136: 172-175Crossref PubMed Scopus (29) Google Scholar whereas another found that adults with moderate to severe AD had high rates of osteopenia and osteoporosis.4Haeck I.M. Hamdy N.A. Timmer-de Mik L. Lentjes E.G. Verhaar H.J. Knol M.J. et al.Low bone mineral density in adult patients with moderate to severe atopic dermatitis.Br J Dermatol. 2009; 161: 1248-1254Crossref PubMed Scopus (33) Google Scholar The present study suggests that AD in adults is associated with lower BMD overall and osteoporosis of the trochanter. In the present study, only a small proportion of adults with eczema and t scores of −2.5 or less reported a physician diagnosis of osteoporosis. This pattern was also seen in adults without eczema, suggesting that osteoporosis in the general population is underdiagnosed. These data suggest that adults with eczema have a higher risk for osteoporosis and would benefit from increased surveillance via DEXA. Patient education and intervention for osteoporosis risk factors appears warranted, including smoking cessation, reduced alcohol consumption, increased weight-bearing activity, vitamin D and calcium supplementation, and even bisphosphonates. Corticosteroid use in patients with eczema might contribute to decreased BMD. However, only a small number of subjects in our study reported current topical or oral corticosteroid use. Furthermore, 2 recent studies suggested that topical corticosteroids have no effect on BMD in moderate to severe AD.6van Velsen S.G. Haeck I.M. Knol M.J. Lam M.G. Bruijnzeel-Koomen C.A. Two-year assessment of effect of topical corticosteroids on bone mineral density in adults with moderate to severe atopic dermatitis.J Am Acad Dermatol. 2012; 66: 691-693Abstract Full Text Full Text PDF PubMed Scopus (15) Google Scholar, 10van Velsen S.G. Knol M.J. van Eijk R.L. de Vroede M.A. de Wit T.C. Lam M.G. et al.Bone mineral density in children with moderate to severe atopic dermatitis.J Am Acad Dermatol. 2010; 63: 824-831Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar Last, comorbid psychological and behavioral disorders and sleep disturbance likely play a role in the risk for all types of injury,2Garg N. Silverberg J.I. Association between eczema and increased fractures, bone or joint injury in adults: a US population-based study.JAMA Dermatol. October 29, 2014; ([Epub ahead of print])https://doi.org/10.1001/jamadermatol.2014.2098Crossref Scopus (46) Google Scholar, 3Garg N. Silverberg J.I. Association between childhood allergic disease, psychological comorbidity, and injury requiring medical attention.Ann Allergy Asthma Immunol. 2014; 112: 525-532Abstract Full Text Full Text PDF PubMed Scopus (97) Google Scholar and therefore likely influence fracture risk as well. Future studies are needed to determine the mechanisms of increased fracture risk in adults with AD. In conclusion, eczema in adults is associated with decreased BMD at the femur and spine, osteoporosis of the trochanter, and increased risk for fractures. Most adults with eczema and osteoporosis were not diagnosed with osteoporosis, suggesting that greater surveillance for osteoporosis is warranted in this high-risk population. Further studies are needed to confirm these associations and determine effective strategies for fracture risk reduction. Table E1Determinants of eczema and fracture in adults∗For multinomial predictors, P values for overall test results are presented. If the overall P value is significant, then individual pairwise tests are also presented.Variable, n (%)Eczema (n = 4972)History of any fracture (n = 4963)NoYesOR (95% CI)P valueNoYesOR (95% CI)P valueAge (y).17<.0001 20-2991.6 (89.5-93.8)8.4 (6.2-10.5)——78.6 (75.4-81.8)21.4 (18.2-24.6)1.00— 30-4994.1 (92.7-95.5)5.9 (4.5-7.3)——71.3 (68.7-73.9)28.7 (26.1-31.3)1.48 (1.18-1.86).0009 50-6992.5 (90.7-94.4)7.5 (5.6-9.3)——60.7 (57.4-63.9)39.3 (36.1-42.6)2.38 (1.89-3.01)<.0001 ≥7093.6 (91.7-95.5)6.4 (4.5-8.3)——54.8 (51.1-58.6)45.1 (41.3-48.9)3.02 (2.37-3.86)<.0001Sex Male94.6 (93.5-95.7)5.4 (4.3-6.5)1.00—64.0 (61.7-66.4)36.0 (33.6-38.3)1.00— Female91.8 (90.4-93.1)8.2 (6.9-9.6)1.56 (1.17-2.06).00271.1 (68.9-73.3)28.9 (26.7-31.1)0.73 (0.63-0.84)<.0001Race<.0001<.0001 White92.2 (91.0-93.3)7.8 (6.7-9.0)1.00—62.6 (60.5-64.7)37.4 (35.3-39.5)1.00— Black93.3 (91.8-94.9)6.7 (5.1-8.2)0.84 (0.62-1.14).2681.1 (78.6-83.5)18.9 (16.5-21.4)0.39 (0.33-0.47)<.0001 Mexican American98.4 (97.5-99.2)1.6 (0.8-2.5)0.20 (0.11-0.35)<.000180.3 (77.6-83.0)19.7 (17.0-22.4)0.41 (0.34-0.50)<.0001 Other Hispanic97.0 (94.0-100)3.0 (0-6.0)0.37 (0.13-1.04).0689.5 (84.5-94.5)10.5 (5.5-15.5)0.20 (0.11-0.34)<.0001 Multiracial/other95.0 (91.5-98.4)5.0 (1.6-8.5)0.62 (0.30-1.31).2175.6 (68.9-82.2)24.4 (17.8-31.1)0.54 (0.37-0.79).001Household income (×$1000) <2094.5 (92.9-96.1)5.5 (3.9-7.1)1.00—66.9 (63.3-70.4)33.1 (29.6-36.7)1.00— ≥2092.7 (91.7-93.8)7.3 (6.2-8.3)1.36 (0.96-1.91).0867.9 (66.1-69.7)32.1 (30.3-33.9)0.95 (0.80-1.14).60Highest level of education.02.08 High school91.6 (89.6-93.5)8.4 (6.5-10.4)1.80 (1.17-2.78).00869.5 (66.2-72.8)30.5 (27.2-33.8)——Body mass index.06.74 <18.596.9 (93.2-100)3.1 (0-6.7)——67.3 (55.0-79.6)32.7 (20.4-45.0)—— 18.5-24.991.6 (89.7-93.4)8.4 (6.6-10.3)——69.2 (66.2-72.2)30.8 (27.8-33.8)—— 25-29.994.4 (93.0-95.8)5.6 (4.2-7.0)——67.7 (64.8-70.5)32.3 (29.5-35.2)—— 30-34.993.2 (91.2-95.1)6.8 (4.9-8.8)——65.5 (61.6-69.3)34.5 (30.7-38.4)—— 35-39.994.0 (91.0-97.0)6.0 (3.0-9.0)——67.8 (62.3-73.3)32.2 (26.7-37.7)—— ≥4090.1 (85.5-94.7)9.9 (5.3-14.5)——65.3 (58.4-72.3)34.7 (27.7-41.6)——Osteoporosis (self-report) No90.9 (86.6-95.2)6.8 (5.9-7.7)1.00—69.0 (67.4-70.7)31.0 (29.3-32.6)1.00— Yes90.9 (86.6-95.2)9.1 (4.8-13.4)1.38 (0.81-2.36).2342.5 (35.4-49.5)57.5 (50.5-64.6)3.02 (2.24-4.08)<.0001Daily prednisone use (>1 mo) No93.1 (92.2-94.0)6.9 (6.0-7.8)1.00—68.8 (67.1-70.5)31.2 (29.5-32.9)1.00— Yes92.3 (88.2-96.5)7.7 (3.5-11.8)1.13 (0.62-2.05).7051.9 (44.5-59.4)48.1 (40.6-55.5)2.04 (1.50-2.77)<.0001GED, General educational development; OR, odds ratio.∗ For multinomial predictors, P values for overall test results are presented. If the overall P value is significant, then individual pairwise tests are also presented. Open table in a new tab Table E2Lack of association between eczema, metabolic factors, and inflammatory factors in adults (n = 4438)VariableNo eczemaEczemaFrequencyPercent (95% CI)FrequencyPercent (95% CI)OR (95% CI)P valueVitamin D (ng/mL) Deficient (<20)186735.6 (33.8-37.3)11036.1 (29.5-42.7)1.19 (0.80-1.78).40 Insufficient (20-29)158242.0 (40.1-43.8)11144.8 (37.8-51.7)1.25 (0.84-1.86).27 Adequate (≥30)75222.5 (20.8-24.1)4819.1 (13.7-24.7)1.00—Calcium (mg/dL) Low ( 10.2)811.8 (1.3-2.3)92.9 (0.7- 5.1)1.61 (0.71-3.68).26Parathyroid hormone (pg/mL) Low (<10)130.2 (0-0.4)00<0.0001 (<0.0001)<.0001 Normal (10-55)321480.1 (78.6-81.5)20476.9 (71.0-82.7)1.00— High (>55)95719.7 (18.3-21.1)6423.1 (17.3-29.0)1.22 (0.87-1.72).23Albumin (g/dL) Low ( 5.4)0000——Alkaline phosphatase (U/L) Low ( 130)1081.4 (1.1-1.8)83.0 (0.6-5.4)2.17 (0.92-5.13).08Lactate dehydrogenase (U/L) Low ( 280)50.1 (0.0-0.1)10.2 (0-0.6)4.25 (0.48-37.58).19CRP (mg/dL) Normal (<1.0)367989.8 (88.7-90.9)23386.5 (81.6-91.3)—— High (≥1.0)51910.2 (9.1-11.3)3613.5 (8.7-18.4)1.38 (0.90-2.12).14WBC (×1000 cells/uL) Low2425.0 (4.2-5.7)155.1 (2.1-8.0)1.03 (0.55-1.94).93 Normal350885.2 (83.9-86.6)22784.2 (79.1-89.4)—— High4629.8 (8.7-10.9)2910.7 (6.2-15.2)1.10 (0.68-1.81).67CRP, C-reactive protein; OR, odds ratio; WBC, white blood cell. Open table in a new tab GED, General educational development; OR, odds ratio. CRP, C-reactive protein; OR, odds ratio; WBC, white blood cell.