Prevalence of Malnutrition and Micronutrient Deficiencies in Older Adults with Ulcerative Colitis

doi:10.21203/rs.3.rs-4669779/v1

Background and Aims: The nutritional status and consequences of malnutrition among older adults with ulcerative colitis (UC) is not known.

Methods: We conducted a single-center, retrospective study of patients 65 years and older with Ulcerative colitis (UC). Malnutrition was defined using the European Society for Clinical Nutrition and Metabolism (ESPEN) definition. Eight micronutrient deficiencies and nutrition-related outcomes were measured. The Saskatchewan Inflammatory Bowel Disease–Nutrition Risk Tool was utilized to identify patients at risk for malnutrition. Data was summarized using descriptive statistics. Characteristics of patients with and without malnutrition were compared using Chi Square test or Fisher’s exact tests (analysis of variance for age) where appropriate.

Results: Two-hundred and ninety patients with a mean age of 73.4 years were included. 54% of patients had moderate to severe UC, with 52% receiving advanced therapy. Fifty-one patients (18%) met criteria for malnutrition, 17% were moderate to high risk for malnutrition, and 87% were low risk. 220 patients (76%) had at least one micronutrient deficiency: 38% vitamin D deficiency, 43% iron deficiency and 11% B12 deficiency. Half of patients had osteoporosis or osteopenia (49%), however, only39% of high-risk patients had undergone a DEXA scan.

Conclusions: Older adults with UC are high risk for malnutrition and micronutrient deficiencies. This population is at particularly high risk for bone-related disease, yet a significant proportion of patients are not undergoing guideline-directed bone density testing. These findings illustrate the need for regular screening for malnutrition, micronutrient deficiency, and bone-related disease in older adults with UC.

Micronutrient

Older adult

Malnutrition

The United States Census Bureau projects that by 2040, 22% of the US population will be over 65.(1) As our population ages, the prevalence of older adults living with ulcerative colitis will continue to rise. For instance, the Crohn’s and Colitis Canada 2023 Inflammatory Bowel Disease (IBD) Impact report predicts that adults over 65 are the fastest growing demographic with IBD. (2) Older adults are a uniquely vulnerable population for malnutrition and its adverse effects due to a myriad of factors including progressive comorbidities, polypharmacy, declining taste and decreased physical activity. (3) Despite this growing cohort, there is little published data on the prevalence and risk factors associated with malnutrition and micronutrient deficiencies in older adults with Ulcerative Colitis (UC). Better understanding of this burden can help guide clinicians and help determine the need and frequency for malnutrition, micronutrient, and bone disease screening. In this present study we aimed to evaluate the prevalence of malnutrition and micronutrient deficiencies among older adults with a diagnosis of UC and investigate the degree of nutrient-related adverse outcomes in this unique patient population.

Study Population

We performed a single center retrospective cohort study at an academic medical center with a well-established Crohn’s and Colitis subspeciality clinic. Patients 65 and older with UC who had been cared for from 2018 − 2023 were identified using a dashboard of IBD patients created with the Tableau software ®. Patients were included if they met the following criteria: age 65 years or older at the time of the study, a confirmed diagnosis of ulcerative colitis based on established clinical and histopathological criteria, availability of comprehensive medical records including recent labs and notes, and presentation to our clinic within the last five years (2018–2023). Exclusion criteria were individuals with insufficient medical records or lack of a confirmed diagnosis of UC. Patients with indeterminate colitis were excluded from the study.

Ethical aspects

This study was approved by the Institutional Review Board (IRB) at the University of California San Francisco (IRB number 23-39463) and was conducted in accordance with the University’s research and patient specific guidelines. All personnel involved in this study underwent CITI Human Subjects Protection Training. As this was a retrospective study, using de-identified data, the requirement for informed consent was waived.

Definitions

Malnutrition was defined using the European Society for Clinical Nutrition and Metabolism (ESPEN) definition(4). To meet criteria, patients had to either have a BMI < 18.5 kg/m² for at least one time point or unintentional weight loss (> 10% of habitual weight indefinite of time, or > 5% over 3 months) and a reduced Body Mass Index (BMI) < 20 kg/m² (if < 70 years old) or reduced BMI of < 22 kg/m² (if > 70 years old). Fat-free mass index was not utilized within our definition of malnutrition given the inability to collect body fat percentage on the majority of our patient population.

The Saskatchewan Inflammatory Bowel Disease Nutrition Risk Tool (SaskIBD-NR)(5) was used to stratify patients into low, medium, and high risk for malnutrition if they did not meet the ESPEN criteria for malnutrition. The full scoring system used for the SaskIBD-NR is included in Supplemental Table 1. All clinical encounter documentation was reviewed to determine patients’ risk of malnutrition based on patient-reported food restrictions, appetite, and symptoms.

Data Collection

A structured data collection process was employed to extract relevant variables from the Electronic Medical Record (EMR). Demographic characteristics included date of birth, gender, and race/ethnicity. Age-related variables such as age at diagnosis of IBD and current age were recorded. Information on the clinical history of UC and comorbidities were collected, noting the presence of conditions such as diabetes mellitus, heart failure, active cancer within the last year, and Primary Sclerosing Cholangitis (PSC). Each comorbidity was documented as a binary variable (present/absent). The year of the last clinic visit was documented to ascertain the duration since the patient was last seen in our clinic. Additionally, the extent of ulcerative colitis was recorded and classified as proctitis, left-sided colitis, or pancolitis based on endoscopic findings or clinical records.

Detailed treatment history for ulcerative colitis was documented, including currently or previously prescribed medications. Long-term use of steroids, defined as usage for more than six months continuously, was recorded separately. Patients’ charts were reviewed for evaluation of 8 common micronutrients within the serum including iron, vitamin B12 (cobalamin), vitamin D, folate, zinc, magnesium, phosphorous and vitamin C (ascorbic acid) (supplemental table 2). Patients were marked as having a deficiency if they were found to be less than the reference value for any specific level since their diagnosis of UC. Lowest documented albumin level and evidence of anemia was also collected. The use of vitamin supplements such as iron, vitamin B12, vitamin D, and calcium was also collected. Patients who required nutrition support including either Total Parenteral Nutrition (TPN) or enteral supplementation were recorded, however, we excluded supplemental nutrition within 90 days of any IBD-related surgery.

Several nutrition-related outcomes were measured including rates of osteopenia, osteoporosis, non-traumatic fracture, development of thrombus (either pulmonary embolism or deep vein thrombosis), colon cancer development, and death. Osteopenia or osteoporosis was documented either based on prior Dual-Energy X-ray Absorptiometry (DEXA) scans or via identified ICD-9 or ICD-10 diagnostic code.

Statistical Analysis

Categorical data was summarized using counts and percentages; age was summarized by its mean and standard deviation. Characteristics of patients with and without malnutrition and those at low, medium, and high risk for malnutrition were compared using univariable logistic regression to determine odds ratio and p-values. Chi-squared test was utilized for p-value calculations for categorical variables and Fisher’s exact test was used for continuous variables as specified within our tables. Patients with missing data were excluded from analysis for each micronutrient or outcome of interest. The results were expressed as odds ratio [ORs] with their corresponding 95% CIs. Statistical significance was set at p < 0.05. Univariable analysis was performed on several variables to adjust for age and comorbidities where appropriate. Additionally, models with interaction terms were performed to control for sex among outcomes related to bone health.

Study population

290/528 patients (55%) met all inclusion criteria and were included in our analysis. The main characteristics of these patients are illustrated in Table 1. The majority of patients were female (56%, n = 161), and 77% (n = 224) were non-Hispanic White, followed by 13% (n = 37) Asian, and 4% (n = 12) Hispanic. The mean age of our patient population was 73.4 years with a median age of 71.8 years. Interestingly, 55% (n = 159) of patients were diagnosed with UC after the age of 50 with a median of 18 years since diagnosis. The average BMI within the population was 26.1 (range 15.7–46.9) and 52% (n = 150) of patients were overweight or obese.

Table 1

Characteristics of Adults ≥ 65 Years of Age with Ulcerative Colitis
Sex (n = 290)
Male	129 (44%)
Female	161 (56%)
Race [n (%)]
Non-Hispanic White	224 (77%)
Asian	37 (13%)
Black	6 (2%)
Hispanic	12 (4%)
Native American	1 (1%)
Other	10 (3%)
Age of Patients [n (median)]	73.4 (71.8)
Mean Age at diagnosis (median age)	51.4 (55)
Years since IBD diagnosis (median)	18.0
Diagnosed after age 50	159 (55%)
Extent of Ulcerative Colitis (n = 271) [n (%)]
Proctitis	24 (9%)
Left Sided Colitis	84 (31%)
Pan-colitis	163 (60%)
Mild to Moderate UC	133 (46%)
Moderate to Severe UC	157 (54%)
Medical Management [n (%)]
Patients who received 5-ASA agents	248 (86%)
Patients who received anti-TNF therapy	49 (17%)
Patients who received anti-integrin therapy	107 (37%)
Patients who received IL-23 inhibitors	26 (9%)
Patients who received JAK inhibitors	11 (4%)
Patients who received sphingosine l-phosphate receptor modulators	2 (1%)
Patients who received > 6 months of steroids	88 (30%)
Patients who received any biologic or small molecule	150 (52%)
Comorbidities [n (%)]
Cancer within the last year	19 (7%)
Heart Failure	21 (7%)
Diabetes	39 (13%)
Primary Sclerosing Cholangitis	13 (4.5%)

Clinical characteristics of patients

The majority of patients within the cohort suffered from extensive and severe UC, with 60% (n = 163) of patients having pancolitis and 54% (n = 157) having moderate to severe UC. Diabetes was the most common co-morbidity (13%, n = 39). Aminosalicylate agents were the most common treatment modality patients were exposed to (86%, n = 248) followed by anti-integrin therapy (n = 107, 37%) and anti-TNF therapy (n = 49, 17%). Thirty percent (30%, n = 88) of patients were exposed to steroids for 6 months or greater at one point during their treatment of IBD and 52% overall (n = 150) had received a biologic or small molecule.

Prevalence of malnutrition and micronutrient deficiencies

Based on the ESPEN definition, 18% (n = 51) of patients met criteria for malnutrition. Among patients who did not meet criteria for malnutrition, 66% (n = 190) were low risk for malnutrition, 11% (n = 31) were moderate risk for malnutrition and 6% (n = 18) were high risk for malnutrition (Table 2).

Table 2

Rates of Malnutrition, Micronutrient Deficiencies & Nutrition-Related Outcomes in the Older Adult Ulcerative Colitis Population
Malnutrition n (% of patients with available data)
Most Recent BMI (average, n = 289)	26.1 (range 15.7–46.9)
BMI < 18.5	12 (4%)
BMI 18.5–24.9	127 (44%)
BMI 25.0-29.9	90 (31%)
BMI 30 or higher	60 (21%)
Meets criteria for malnutrition¹	51 (18%)
Low risk for malnutrition (SaskIBD-NRT)²	190 (66%)
Moderate risk for malnutrition (SaskIBD-NRT)²	31 (11%)
High risk for malnutrition ((SaskIBD-NRT)²	18 (6%)
Age Distribution of Patients with Malnutrition [n (%)]
65–69	99 (34%)
70–74	79 (27%)
75–79	62 (22%)
80–84	35 (12%)
85–89	9 (3%)
> 90	6 (2%)
Markers of Malnutrition [n (%)]
Low Albumin	90 (35%)
Anemia (hemoglobin < 12.5)	151 (56%)
Required enteral nutrition since diagnosis	8 (2.7%)
Required Total Parental Nutrition since diagnosis	10 (3.5%)
Vitamin Deficiencies³ [n (%)]
Iron deficient (defined by ferritin < 50, T sat < 20%, serum iron < 150, TIBD < 290)	97 (43%)
Low Vitamin D	88 (38%)
Low Magnesium	38 (22%)
Low Phosphorous	25 (19%)
Low Vitamin C	7 (17%)
Low Vitamin B12	23 (11%)
Low Zinc	3 (6%)
Low Folate	6 (5%)
Number of patients with at least one vitamin deficiency	220 (76%)
Vitamin Supplementation [n (%)]
Iron supplementation	74 (26%)
Vitamin D	172 (60%)
Vitamin B12	63 (33%)
Calcium	102 (36%)
Nutrition Related Outcomes [n (%)]
Osteopenia in females	70 (24%)
Osteopenia in males	23 (8%)
Osteoporosis in females	39 (13%)
Osteoporosis in males	9 (3%)
Non-Traumatic fracture in females	25 (9%)
Non-Traumatic fracture in males	15 (5%)
DEXA scan performed in females	90 (56%)
DEXA scan performed in males	31 (24%)
DEXA scan performed in patients on long term steroids (> 6 months)	34 (39%)
Thrombus development after IBD diagnosis	25 (8.7%)
Colon cancer development	10 (3.4%)
¹ Based on ESPEN criteria for malnutrition (BMI < 18.5 or unintentional weight loss > 10% of body weight in any time or > 5% over 3 months in addition to BMI < 20 or < 22 in those < 70 years of age and in those > 70 years of age respectively; did not include fat free mass as a criteria option due to lack of data)
² Saskatchewan Inflammatory Bowel Disease–Nutrition Risk Tool
³ Percent of each deficiency measured based on only patients with available data

Albumin and evidence of anemia were used as surrogate markers for inflammation and evidence of malnutrition. Fifty-six percent of patients were found to be anemic (n = 151) and 35% (n = 90) of patients had a low albumin. Only 3.5% of patients (n = 10) required total parental nutrition since their diagnosis of UC and 2.7% of patients (n = 8) required enteral nutrition.

In total, 76% (n = 220) of patients were found to have at least one vitamin deficiency (Table 2). Percentages of each vitamin deficiency only included patients who had laboratory data available for analysis. The most common deficiency was iron (43%, n = 97/223), followed by vitamin D (38%, n = 88/231), magnesium (22%, n = 38/168), phosphorous (19%, n = 25/134) and vitamin B12 (11%, n = 23/206) (Fig. 1; Supplemental Table 3). Approximately 26% (n = 74) of patients had taken iron supplementation, 60% of patients (n = 172) had taken vitamin D supplementation, 36% (n = 102) had taken calcium and 33% (n = 63) had taken vitamin B12.

Rate of nutrition-related outcomes

Bone-related disease was defined as osteopenia or osteoporosis. This was the most common nutrition-related outcome measured. In total 49% of patients (n = 140) either had osteopenia (n = 93, 32%) or osteoporosis (n = 48, 17%). Additionally, 14% (n = 40) had experienced a non-traumatic fracture. Among patients with at least 6 months of steroid exposure, only 39% (n = 34) of patients had undergone a DEXA scan. Thrombus was diagnosed in 8.7% of patients (n = 25) and colon cancer in 3.4% of patients (n = 10).

Predictive factors for risk of malnutrition

In evaluating patient specific factors that increase one’s risk of malnutrition based on the SaskIBD-NR tool, heart failure (OR 2.90, CI 1.04–8.05, p-value < 0.04), cancer (OR 3.07, CI 1.01–9.30, p-value < 0.040), and severity of UC (OR 2.83, CI 1.43–5.58, p-value < 0.003) were found to significantly increase the risk of malnutrition while diabetes and PSC were not individually found to increase the risk (Table 3). In regard to the impact of specific treatment modalities on a patient’s risk of malnutrition, only anti-integrin (OR 2.47, CI 1.30–4.69, p-value < 0.006) and IL-23/IL-12 inhibitor biologics (OR 3.28, CI 1.29–8.32, p-value < 0.01) were found to be associated with a higher risk of malnutrition (Table 3). When age and comorbidities were controlled for, both agents continued to be associated with an increased risk of malnutrition (Table 3).

Table 3

Association Between Patient Characteristics and Risk of Malnutrition
Characteristic	Low Malnutrition Risk		Moderate/high Malnutrition Risk		OR	95% CI	p-value
Characteristic	N	(%)	N	(%)	OR	95% CI	p-value
Age, mean (SD)	72.9	(5.9)	74.1	(5.9)	1.03	(0.98, 1.09)	0.200
BMI [continuous]	26.9	(4.7)	27.2	(6.0)	1.01	(0.95, 1.07)	0.770
BMI [categorical]
Normal (18.5–24.9)	78	(41.5)	19	(38.0)	Ref
Overweight (25-29.9)	62	(33.0)	21	(42.0)	1.39	(0.69, 2.81)	0.360
Obese (30+)	48	(25.5)	10	(20.0)	0.85	(0.37, 1.99)	0.720
Cancer¹
	8	(4.3)	6	(12.0)	3.07	(1.01, 9.30)	0.040
Heart failure
	10	(5.3)	7	(14.0)	2.90	(1.04, 8.05)	0.040
Diabetes
	24	(12.8)	9	(18.0)	1.5	(0.65, 3.47)	0.340
PSC
	6	(3.2)	3	(6.0)	1.94	(0.47, 8.03)	0.360
Any comorbidity
	43	(22.9)	20	(40.0)	2.25	(1.16, 4.35)	0.016
Severity of ulcerative colitis
Mild	99	(52.4)	14	(28.0)	Ref
Moderate to severe	90	(47.6)	36	(72.0)	2.83	(1.43, 5.58	0.003
Treatment with any anti-TNF biologics
	64	(34.0)	21	(42.9)	1.45	(0.76, 2.76)	0.250
Treatment with 5-ASA
	168	(89.4)	39	(79.6)	0.46	(0.20, 1.07)	0.070
Treatment with Thiopurine
	41	(21.8)	10	(20.4)	0.92	(0.42, 2.00)	0.830
Treatment with Methotrexate
	11	(5.9)	5	(10.2)	1.83	(0.60, 5.53)	0.290
Treatment – with anti-integrin
	59	(31.4)	26	(53.1)	2.47	(1.30, 4.69)	0.006
Treatment with anti-integrin therapy (controlled for age & comorbidity)					2.81	(1.44,5.47)	0.002
Treatment with IL23 inhibitor
	12	(6.4)	9	(18.4)	3.28	(1.29, 8.32)	0.010
Treatment with IL23 inhibitor (controlled for age & comorbidity					3.51	(1.36,9.07)	0.010
Treatment with JAK inhibitors
Yes	5	(2.7)	2	(4.1)	1.56	(0.29, 8.28)	0.600
Treatment with Ozanimod
	0	0	0	0	0	0	0.00
Long-term steroid use
	51	(27.0)	17	(34.7)	1.44	(0.73, 2.81)	0.290

¹ Cancer defined as clinically active within the last year; Associations significant at the α ≤ 0.05 level are bolded for emphasis

Table 4: Association Between Risk of Malnutrition and Nutrition-Related Outcomes

Characteristic	Low Risk		Moderate/High Risk		OR	95% CI	p-value
Characteristic	N	(%)	N	(%)	OR	95% CI	p-value
Osteopenia
	57	(30.5)	17	(34.0)	1.17	(0.60, 2.28)	0.630
Osteoporosis
	27	(14.4)	7	(14.0)	0.96	(0.39, 2.36)	0.940
Any bone disease
	77	(41.2)	21	(42.0)	1.03	(0.55, 1.95)	0.920
Non-traumatic fracture
	19	(10.2)	8	(16.0)	1.67	(0.68, 4.09)	0.260
Non-traumatic Fracture when controlling for sex					11.58	(1.06,126)	0.045
Iron deficiency¹
	48/139	(34.5)	25/40	(62.5)	3.15	(1.52, 6.55)	0.002
Vitamin D deficiency¹
	55/141	(39.0)	15/45	(33.3)	0.78	(0.38, 1.58)	0.490
Vitamin B12 deficiency¹
	13/126	(10.3)	4/37	(10.8)	1.05	(0.32, 3.45)	0.930
Thrombus development
Yes	13	(6.9)	3	(6.3)	0.90	(0.25, 3.30)	0.880
Any micronutrient deficiency
Yes	121	(68.8)	38	(79.2)	1.73	(0.80, 3.71)	0.160

¹ Not all patients were tested; denominators reflect actual observations available; Associations significant at the α≤0.05 level are bolded for emphasis.

Among patients who met criteria for malnutrition (Supplemental Table 4), only BMI was found to be associated with risk of malnutrition, with a higher BMI being protective of malnutrition (OR 0.70, CI 0.63–0.79, p-value < 0.001). Given the limited variables found to be significantly associated with malnutrition, multi-variable analysis was not performed.

Association Between Malnutrition and Nutrition-Related Outcomes

Iron deficiency (OR 3.15, CI 1.52–6.55, p-value < 0.002) was found to be associated with patients at higher risk for malnutrition. Additionally, when stratified by sex, women who were higher risk for malnutrition were more likely to have a bone fracture (p-value < 0.02), however this was not identified in men (Table 4).

Patients who met criteria for malnutrition were found to be at higher risk of osteoporosis (OR 2.26, CI 1.11–4.61, p-value < 0.025), any bone-related disease (either osteopenia or osteoporosis) (OR 2.60, CI 1.38–4.88, p-value < 0.003) and non-traumatic fracture (OR 2.85, CI 1.26–5.59, p-value < 0.01) (Table 5). This did not vary based on sex. Additionally, patients with malnutrition had approximately 3 times higher risk of thrombus development (OR 2.96, CI 1.27–7.14, p-value < 0.016) and 2 times higher risk of at least one micronutrient deficiency (OR 2.20, CI 0.98–4.93, p-value < 0.056).

Table 5: Associations Between Malnutrition and Nutrition-Related Outcomes

Characteristic	OR	95% CI	p-value
Characteristic	OR	95% CI	p-value
Age, mean (SD)	1.02	(0.98, 1.08)	0.210
Osteopenia	1.31	(0.70, 2.46)	0.400
Osteoporosis	2.26	(1.11, 4.61)	0.025
Any bone disease (osteopenia or osteoporosis)	2.60	(1.38, 4.88)	0.003
Non-traumatic fracture	2.85	(1.26, 5.59)	0.010
Iron deficiency¹	1.74	(0.90, 3.38)	0.100
Vitamin D deficiency¹	1.10	(0.57, 2.15)	0.770
Vitamin B12 deficiency¹	1.43	(0.53, 3.89)	0.480
Thrombus development	2.96	(1.27, 7.14)	0.016
Any micronutrient deficiency	2.20	(0.98, 4.93)	0.056

¹Not all patients were tested; denominators reflect actual observations available; Associations significant at the α≤0.05 level are bolded for emphasis.

In this retrospective study older adults with ulcerative colitis had an 18% rate of malnutrition. Three-quarters of patients had at least one vitamin deficiency and almost half had bone-related disease. Among patients with malnutrition, they were more likely to have osteoporosis, non-traumatic fracture, at least one micronutrient deficiency and thrombus development. To our knowledge, this is the first retrospective cohort study that has evaluated the prevalence of malnutrition and micronutrient deficiencies among this rapidly expanding older adult population with ulcerative colitis.

Malnutrition

In comparing our findings to previous studies that did not specifically look at the older adult population, our average BMI of 26.1 (range 15.7–46.9) was higher than previous reports with 52% of the population being overweight or obese. This likely skewed our prevalence rate of malnutrition down as we were unable to appropriately account for sarcopenia in overweight patients without fat-free mass calculations. A recent study from China examining 420 patients age 18–72 with UC found a much higher 38% rate of malnutrition within their population(6). However, their reported mean BMI was 20.41 with only 5.7% of their population meeting criteria for an overweight BMI. In comparing our study to a prospective multicenter Spanish cohort of 510 patients with UC and more similar distribution of BMI to our population(7), they found a malnutrition rate of 14%. Furthermore, while standardization of malnutrition diagnosis with the ESPEN criteria across the literature is helpful, there are several inherent weaknesses with the reliance of BMI as one of the primary diagnostic criteria. Malnutrition can manifest across the weight spectrum including those with overweight and obese BMIs. BMI does not reflect adiposity or body composition well and is not representative of a diverse patient demographic, likely underestimating certain groups’ excess adiposity(8).

Micronutrient deficiencies

Micronutrient deficiency is often considered an indirect marker of malnutrition as this suggests insufficient nutrient consumption either due to poor absorption or low nutrient intake. In this retrospective review, iron (43%, n = 97) was found to be the most common micronutrient deficiency, which parallels the current literature in the general UC population(9, 10). Vitamin D (38%, n = 88) was the second most common deficiency, followed by magnesium (22%, n = 38) and phosphorous (21%, n = 25). A limitation to our findings was the low rate at which some of the micronutrients were examined. For instance, only 16.6% percent of patients had a plasma zinc, 14.4% plasma ascorbic acid (vitamin C), and 79.7% plasma vitamin D checked. This is concerning given the known association between low levels of these micronutrients and risk of IBD flare and poor wound healing. Zinc deficiency has specifically been associated with more severe colitis and higher likelihood of surgery(11, 12).

Our study illustrates that older patients with UC continue to have a high burden of deficiencies that would benefit from regular screening and repletion, particularly as they continue to age and develop comorbidities that place them at higher risk for poor appetite and decreased nutrient intake. Furthermore, we agree with the recent AGA 2024 recommendation to screen all patients with IBD for vitamin D and iron deficiency(13) as our patient population demonstrated a high burden of disease that not only impacts their disease progression but quality of life.

Vitamin D is a particularly important micronutrient to monitor in older adults as people become progressively higher risk for osteopenia, osteoporosis, and fracture with age. There is also emerging data that vitamin D plays an important role in controlling chronic inflammation(14, 15) and repleting low levels may improve IBD outcomes. Within our population, 80% of patients had undergone vitamin D testing and 60% of patients were taking Vitamin D supplementation (accounting for both treatment dosing and maintenance dosing). According to the most recent Center for Disease Control data, 2.9% of adults over age 60 in the general population were found to have vitamin D deficiency(16), illustrating an almost 12 times higher rate of deficiency in older adults with UC compared to older adults without UC. Our study further demonstrates the importance of careful screening and treatment of this micronutrient deficiency.

Bone-Related Disease

Within this cohort, 49% of patients either had osteopenia (32%) or osteoporosis (17%) with another 14% of patients suffering from a non-traumatic fracture (14%) (Table 2). The rate of osteoporosis within this study was similar to the United States general population of adults over the age of 65, currently reported to be 17.7%(17). However, we suspect our prevalence of osteoporosis is under-reported as only 39% of those > 65 years old with more than 6 months of steroid use had undergone a DEXA scan despite current recommendations(18). These findings suggest a significant opportunity to improve the quality of care we are providing our patients.

While there is currently no clear consensus among the United States and European IBD guidelines on the optimal screening start age and frequency for bone density screening for IBD patients(18, 19), we advise clinicians to have a low threshold to pursue bone density screening irrespective of age, in patients with malnutrition or additional risk factors that place patients at higher risk for bone disease such as a history of prolonged steroid use or vitamin D deficiency. Additionally, per the current National Osteoporosis Foundation recommendations, all women over 65 years of age and men over 70 years old should undergo DEXA testing(20). Once identified, quality measures should be put in place to ensure patients are appropriately treated to prevent non-traumatic fracture. This study provides support for aggressive bone density screening given the prevalence of bone-related disease in this older IBD population.

Factors associated with higher risk of malnutrition

Heart failure, cancer, and severity of UC were found to be associated with higher risk for malnutrition, while PSC and diabetes were not. These findings demonstrate that IBD providers must take into consideration a patient’s comorbidities when risk stratifying patients for malnutrition and have a low threshold to refer patients to a dietitian specialized in GI conditions for dietary optimization.

In examining how a patient’s medical therapy impacted their risk of malnutrition, we found that both anti-integrin and IL-23 inhibitors were associated with a higher risk for malnutrition. Given the favorable safety profile of these agents, we suspect that physicians preferentially chose these biologics for patients with factors that inherently placed them at higher risk for malnutrition, however, when we controlled for age and comorbidities, both anti-integrin and IL-23 Inhibitors continued to be associated with risk of malnutrition (Table 3).

Outcomes associated with malnutrition

As seen in Table 5, we found that patients who met criteria for malnutrition were more likely to develop osteoporosis, non-traumatic fracture, and thrombus development. These findings are consistent with prior studies not specific to the older adult UC population that have identified malnutrition as a risk factor for venous thromboembolism(21) and overall increased mortality(22, 23). Patients who are identified as having malnutrition should undergo more extensive micronutrient and bone density monitoring to prevent further nutrition-related complications.

Limitations

Limitations inherent in retrospective studies, including potential selection bias, reliance on available medical records, and the inability to establish causality, should be considered in the interpretation of this study’s results. The rate of screening for bone density loss and micronutrient deficiencies may be underestimated in our study given inability to access complete medical records from other institutions for some patients. Additionally, the prevalence of micronutrient deficiencies among our patient population was skewed by the limited availability of serum levels of some micronutrients that are less commonly tested (Supplemental Table 2). These include zinc, vitamin C and folate. We were also unable to assess the temporality consistently and accurately between a low micronutrient lab value and initiation of a nutritional supplement that may have resulted in under estimation of some vitamin deficiencies.

Given the lack of consistent body fat percentile available within the electronic medical record, we were unable to use a fat-free mass index as one of the criteria for malnutrition. This likely underreported our prevalence of malnutrition given our high percentage of patients who were overweight or obese. Moving forward, prospectively following a cohort of younger adults with UC and collecting data on their body composition, micronutrients and bone health as they continue to age would allow us to better understand how body composition and malnutrition risk progresses with age.

This was the first study to examine the prevalence of malnutrition and micronutrient deficiencies as well as nutrition-related complications in adults over 65 with ulcerative colitis. The prevalence of malnutrition was notable, with 18% of patients meeting criteria, emphasizing the need for heightened clinical awareness in managing this aging population. Moreover, three-quarters of the cohort exhibited at least one vitamin deficiency underscoring the importance of regular screening and tailored nutrition interventions for this older population. This study also illuminates the elevated risk of bone-related diseases in this demographic, with nearly half of the patient’s experiencing osteopenia or osteoporosis. These findings prompt the necessity for comprehensive annual vitamin D assessments, especially given the 12 times higher rate of vitamin D deficiency in this older UC patient group than the general population. As the study highlights the association between malnutrition and adverse outcomes such as osteoporosis, fractures, and thrombus development, future research should delve into refining nutrition interventions and assessing the evolving body composition of older adults with UC. To mitigate the effect of malnutrition and micronutrient deficiencies in this population, it will be imperative to develop and implement strong consensus guidelines on bone density screening procedures for the older IBD population. Combining nutritional assessment and intervention with standard drug therapy will lead to safer and more effective management of our IBD patients.

Inflammatory Bowel Disease (IBD); Ulcerative Colitis (UC); European Society for Clinical Nutrition and Metabolism (ESPEN; Body Mass Index (BMI); Saskatchewan Inflammatory Bowel Disease Nutrition Risk Tool (SaskIBD-NR); Electronic Medical Record (EMR); Primary Sclerosing Cholangitis (PSC); Total Parenteral Nutrition (TPN); Dual-Energy X-ray Absorptiometry (DEXA)

Conference presentation: Presented at Digestive Disease Week 2024 (Washington DC, USA)

All authors have made substantial contributions to all of the following: (1) the conception and design of the study, or acquisition of data, or analysis and interpretation of data, (2) drafting the article or revising it critically for important intellectual content, (3) final approval of the version to be submitted.

Authors’ contributions: All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Zoe Memel, Anna Thiemann, Cooper Dort and Kendall Beck. The first draft of the manuscript was written by Zoe Memel and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

This manuscript has not been previously published and is not under consideration elsewhere.

Financial Disclosures/Conflicts of Interest:

ZM – Consultant for Neptune Medical. AT – none. CD – none. UM – Consultant: Abbvie, Bristol Myers Squibb, Boeringher Ingelheim, Celltrion, Enveda, Gilead, Janssen, Lilly, Merck,Pfizer, Protagonist, Rani Therapeutics, Roivant, Takeda

KB – Site- specific Principle Investigator for AbbVie, Gilead, and NorthSea Clinical Trials.

Data Transparency Statement: Study materials used for this manuscript can be available to researchers upon request.

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No competing interests reported.

SupplementalTables.docx

Prevalence of Malnutrition and Micronutrient Deficiencies in Older Adults with Ulcerative Colitis

Status:

Journal Publication

Version 1

Abstract

Figures

Introduction

Methods

Study Population

Ethical aspects

Definitions

Data Collection

Statistical Analysis

Results

Study population

Clinical characteristics of patients

Prevalence of malnutrition and micronutrient deficiencies

Rate of nutrition-related outcomes

Predictive factors for risk of malnutrition

Association Between Malnutrition and Nutrition-Related Outcomes

Discussion

Malnutrition

Micronutrient deficiencies

Bone-Related Disease

Factors associated with higher risk of malnutrition

Outcomes associated with malnutrition

Limitations

Conclusions

Abbreviations

Declarations

References

Additional Declarations

Supplementary Files

Status:

Journal Publication

Version 1