Height loss with age in adults with Prader-Willi syndrome may result in artifactual increases in BMI

Height loss with age in adults with Prader-Willi syndrome may result in artifactual increases in BMI | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Height loss with age in adults with Prader-Willi syndrome may result in artifactual increases in BMI Harry Hirsch, Harel Arzi, Fortu Benarroch, Varda Gross-Tsur This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6064456/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 17 Apr, 2025 Read the published version in Scientific Reports → Version 1 posted 6 You are reading this latest preprint version Abstract Modest decreases in height occur during normal aging, but usually have only a minimal effect on BMI (body mass index). Height loss may result from vertebral fractures, disc collapse, kyphosis, and/or scoliosis. Accurate determinations of BMI values are essential for prescribing diet and exercise regimens especially for adults with Prader-Willi syndrome (PWS). We measured standing heights in 28 PWS adults over a duration 11.3 ± 3.4 (range 5.1 to 16.2) years in our national multidisciplinary PWS clinic. Most had no or only minimal height loss, but in four individuals measured heights decreased by 6.2, 6.6, 7.0, and 6.3 cm, respectively. Height loss for these four patients resulted in artifactually high BMI values compared to values based on heights measured 7.9 to 16.1 years earlier. The apparent increase in BMI due to height loss rather than weight gain may lead to inappropriate recommendations for reduction in caloric intake. Even minor changes in diet restrictions can affect mood and behavior in individuals with PWS. Recognition of height loss as a contributing factor to BMI calculations is important for clinical studies evaluating effects of life-style changes and medical interventions for obesity. Health sciences/Diseases Health sciences/Diseases/Metabolic disorders Biological sciences/Genetics/Clinical genetics Introduction Body mass index (BMI) [weight in kg/(height in m) 2 ] is the most commonly used measure of obesity in children and adults. BMI values classify adults as overweight (≥ 25.0 to 29.9kg/m 2 ), obesity class I (30.0–34.9 kg/m 2 ), obesity class II (35.0–39.9 kg/m 2 ), or obesity class III (≥ 40kg/m 2 )[ 1 ]. Prader-Willi syndrome (PWS) results from deletion or lack of expression of specific genes on the paternal chromosome 15 and is associated with severe obesity due to lack of satiety and severe hyperphagia [ 2 ]. Individuals with PWS require strict control of diet and exercise in order to prevent weight gain and complications of morbid obesity. For these patients, even minor changes in BMI, may lead to recommendations for either increasing or decreasing daily caloric intake and/or changes in exercise regimens in order to prevent excessive weight gain. Normal aging is usually associated with modest decreases in standing height and has only a minimal effect on BMI values [ 3 ]. Height loss may result from vertebral fractures, disc collapse, or kyphoscoliosis. Accurate measurements of standing heights in adults with PWS are sometimes difficult to attain due to the high prevalence of kyphoscoliosis, hypotonia and poor posture in this population [ 4 – 5 ]. An apparent decrease in height measurements will result in an increased BMI value, even when the person's weight has not changed. Methods and study population We studied, retrospectively, all 28 adults (mean age 35.9 ± 5.3 years at the latest follow-up visit) with genetically confirmed PWS who were followed in our multidisciplinary national PWS clinic for at least five years after the age of 20 years. Standing height was measured by a trained clinic assistant using a wall-mounted stadiometer. Patients were measured without shoes and weighed in light clothing. If the measured height differed by more than 1 cm, the height measurement was repeated by a pediatric endocrinologist (HJH). We compared the tallest height (H-1) recorded after age 20 years (mean age 24.7 ± 3.6 years) with the height (H-2) at the latest clinic visit (mean age 35.9 ± 5.3 years). Mean duration of follow-up was 11.3 ± 3.4 (range 5.1 to 16.2) years. Written informed consent was obtained from study participants and parents or guardians as part of an ongoing study of growth and development which was approved by the institutional review board of the Shaare Zedek Medical Center, Jerusalem. All study protocols were carried out in accordance with relevant guidelines and regulations. The datasets used and analysed during the current study are available from the corresponding author on reasonable request. Results Three individuals had no loss of height and seven had a slight gain in height (mean gain 1.6 cm, range 0.5–2.7 cm). Fourteen patients had mild height loss (H-2 minus H-1) of 1.9 ± 0.8 cm over a duration of 10.9 ± 3.8 years. Standing height measurements for four patients consistently decreased at yearly visits and at a mean age of 35.6 ± 5.5 years were significantly shorter than the measured heights at age 23.1 ± 3.3 years (Table 1 ). BMI values using the latest measured heights (H-2) were increased compared to the values calculated by using their “true” heights (H-1) by 3.8, 2.8, 2.5, and 2.4 kg/m2, respectively and as shown in Table 1 . Table 1 BMI values for four individuals with Prader-Willi syndrome and height loss Pt. 1 Pt. 2 Pt. 3 Pt. 4 Age (years)at latest measurement 42.5 32.4 37.1 30.2 Sex F M F M PWS genotype IC UPD DEL DEL Duration of follow-up (yrs) 15.7 7.9 16.1 10.1 H-1 (cm) 152.0 142.6 148.5 145.5 H-2 (cm) 145.8 136.0 141.5 139.2 Height loss (cm) -6.2 -6.6 -7.0 -6.3 BMI (kg/m2) for measured height 41.7 31.9 31.0 27.2 BMI (kg/m2) for estimated "true" height 37.9 29.1 28.5 24.8 Table legend: BMI values for the four adults with PWS whose measured heights decreased significantly. PWS genotypes: IC, imprinting center defect; UPD, uniparental disomy; DEL, deletion. H-1 is the tallest height measured after age 20 years. H-2 is the height measured at the latest clinic visit. Height loss is the value of H-2 minus H-1. BMI (weight in kg/[height in m] 2 ) values were calculated using the weight at the latest clinic visit, height at the latest clinic visit (H-2), and then recalculated assuming "true" height (H-1) . We reviewed the medical records of these four patients, who are at the highest risk for a potential increase of BMI value, even without any weight gain, and to try to understand why they underwent a greater loss of height compared to the overall group. On x-ray examination at age 41 years, patient #1 had compression fractures seen in vertebrae L-1 to L-5. Although patient #2 had severe kyphosis, he underwent fusion of nine or more vertebrae and vertebral osteotomy which would have been expected to increase his height. Patient #3 had osteoporosis (Z-score for lumbar spine was − 3.2) but did not have documented vertebral fractures. At age 27 years, x-rays of patient #4 showed scoliosis of 41 degrees and kyphosis of 40 degrees. BMI values calculated according to the latest measured heights were significantly higher than the BMI values determined using H-1 measurements as the assumed "true" heights, as shown in table one. After adjusting BMI values to compensate for height loss, patient #1 was reclassified as obesity class II vs obesity class III, two patients were reclassified as being people with overweight instead of being people with obesity, and the reduced BMI value for patient 4 was in the borderline normal range. Discussion The causes of severe height loss in adults with PWS are most likely multifactorial and may not always be attributed to a specific orthopedic diagnosis. Nevertheless, the consistent decrease in measured heights in four individuals resulted in higher values of BMI for the same weight compared to BMI values using their "true" height for the calculation. Accurate measurements of standing height may be difficult in some individuals with PWS due to hypotonia, kyphoscoliosis, and poor posture. Nevertheless, for most adults followed in our clinic, recorded heights were stable with minimal or no height loss over five to 16 years of follow-up. Therefore, the consistent and gradual decrease in measured heights for the four individuals with significant height loss cannot be attributed to improper measuring technique. Sorkin et al described cumulative height losses of approximately 5 cm for men and 6 cm for women from young adulthood to"old age," based on three epidemiologic population studies (7). The impact of height loss on increasing BMI was relatively small, however, in the range of 1.5 kg/m 2 . In contrast to a general population, even minor increases in BMI are significant for individuals with PWS. The apparent increase in BMI due to height loss rather than due to weight gain, may lead to inappropriate recommendations for caloric intake and exercise regimens. Some guidelines for individuals with PWS use height as one of the criteria for prescribing the recommended daily caloric intake: 10–14 kcal/cm of height for weight maintenance and 7–8 kcal/cm of height for weight loss [ 6 ]. In our group homes dedicated specifically for individuals with PWS, typical diets provide 1400 kcal/day for weight maintenance. When weight and/or BMI increases, caloric intake is reduced to 1200 kcal/day. Recognition of the effect of height loss in aging is important for individual nutritional guidance in order to avoid unnecessary reduction in caloric intake. In our multidisciplinary PWS clinic, we follow our patients from adolescence through adulthood, including yearly height measurements. Therefore, we were able to recognize that the apparent increase in BMI in these four individuals was due to height loss and not to excessive weight gain. For individuals with Prader-Willi Syndrome, even minor dietary changes, can significantly affect their mood and behavior. For example, we describe two patients with PWS who gained weight and whose BMI truly increased, not due to height loss, who displayed strong emotional responses when they were told to decrease their caloric intake. During a routine visit in our multidisciplinary PWS clinic, a 43 year- old woman became very distressed when told that she had gained weight. When recommendations to reduce caloric intake were discussed, she became very upset, started crying, and abruptly ran out of the room, slamming the door. She stood outside, shouted, and refused to participate in any further discussion or examinations. When a 26-year-old man with PWS was told by his dietitian that he needed to reduce his caloric intake by 100 kcal/day because of weight gain, he became very agitated. He started cursing, physically threatened the dietitian and broke his own glasses. In conclusion, recognizing the impact of height loss on BMI is essential for providing appropriate nutritional guidance and avoiding unnecessary reductions in caloric intake. Records of previous height measurements should be made available especially when individuals with PWS are transitioned from pediatric or adolescent centers to adult clinic settings. Additionally, attention to the impact of height loss on BMI may be important for research studies evaluating the effects of lifestyle changes and medical interventions for obesity, not only for individuals with PWS. Declarations Author Contribution H.J.H. collected and analyzed the patient data, wrote the main manuscript; H.A. provided orthopedic consultations and reviewed the manuscript; F.B. reviewed and recommended revisions of the manuscript; V.G.T. collected patient data, contributed to writing and reviewing the manuscript. Acknowledgement We wish to thank Miriam Attia for organizing and collecting data from the medical records and Dorit Forer, clinical dietitian, for sharing her experience with providing nutritional guidance to our patients with PWS. Data Availability The datasets used and analysed during the current study are available from the corresponding author upon reasonable request. References Fryar, C. D., Carroll, M. D. & Afful, J. Prevalence of overweight, obesity, and severe obesity among adults aged 20 and over: United States, 1960–1962 through 2017–2018 (NCHS Health E-Stats, 2020). Angulo, M. A., Butler, M. G. & Cataletto, M. E. Prader-Willi syndrome: a review of clinical, genetic, and endocrine findings. J. Endocrinol. Invest. 38 (12), 1249–1263. 10.1007/s40618-015-0312-9 (2015). Epub 2015 Jun 11.PMID: 26062517. Sorkin, J. D., Muller, D. C. & Andres, R. Longitudinal change in height of men and women: implications for interpretation of the body mass index: the Baltimore Longitudinal Study of Aging. Am J Epidemiol. ;150(9):969 – 77. (1999). 10.1093/oxfordjournals.aje.a010106 . PMID: 10547143. Crinò, A. et al. High Prevalence of Scoliosis in a Large Cohort of Patients with Prader-Willi Syndrome. J. Clin. Med. 11 (6), 1574. 10.3390/jcm11061574 (2022). van Bosse, H. J. P. & Butler, M. G. Clinical Observations and Treatment Approaches for Scoliosis in Prader-Willi Syndrome. Genes (Basel) . 11 (3), 260. 10.3390/genes11030260 (2020). Hoffman, C. J., Aultman, D. & Pipes, P. A nutrition survey of and recommendations for individuals with Prader-Willi syndrome who live in group homes. J. Am. Diet. Assoc. 92 (7), 823–830 (1992). 833.PMID: 1624651. Sorkin, J. D., Muller, D. C. & Andres, R. Longitudinal Change in the Heights of Men and Women: Consequential Effects on Body Mass Index. Epidemiol. Rev. 21 (2), 247–260. 10.1093/oxfordjournals.epirev.a018000 (1999). Additional Declarations No competing interests reported. Supplementary Files heightlossinPWStable1.docx Cite Share Download PDF Status: Published Journal Publication published 17 Apr, 2025 Read the published version in Scientific Reports → Version 1 posted Editorial decision: Accepted 14 Apr, 2025 Reviews received at journal 27 Mar, 2025 Reviewers agreed at journal 26 Mar, 2025 Reviewers invited by journal 25 Mar, 2025 Submission checks completed at journal 24 Mar, 2025 First submitted to journal 21 Mar, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6064456","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":433689179,"identity":"16f9e5bc-d72e-4eec-9598-efe307e35a1c","order_by":0,"name":"Harry Hirsch","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAyElEQVRIiWNgGAWjYBACA2YgwdjAwNgP4iUUkKJlZgNIiwExWhigWjYcgHMJAHN23scffu7YJrv5/OrEDw8MGOT5xQ7g12LZzG4m2XvmtvG2G283SwAdZjhzdgIBhx1mY2NmbLuduO3G2Q0gLQkGtwlrYf4M0rJ5xtnNP4jVwiAN0rKBv3cb0bawSfa23TaecYN3m0WCgQQRfjl/jPnDz7bbsv39Zzff/FFhI88vTUALAkiAVUoQqxwE+A+QonoUjIJRMApGEgAABTBH11HWXeAAAAAASUVORK5CYII=","orcid":"","institution":"Shaare Zedek Medical Center","correspondingAuthor":true,"prefix":"","firstName":"Harry","middleName":"","lastName":"Hirsch","suffix":""},{"id":433689181,"identity":"11590b5b-e4ab-4dd7-810b-cd1277959c70","order_by":1,"name":"Harel Arzi","email":"","orcid":"","institution":"Shaare Zedek Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Harel","middleName":"","lastName":"Arzi","suffix":""},{"id":433689182,"identity":"90061852-e14f-415e-9a56-396f57bef2db","order_by":2,"name":"Fortu Benarroch","email":"","orcid":"","institution":"The Hebrew University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Fortu","middleName":"","lastName":"Benarroch","suffix":""},{"id":433689184,"identity":"6f280a06-46ad-4e98-8a85-d653028fe565","order_by":3,"name":"Varda Gross-Tsur","email":"","orcid":"","institution":"Shaare Zedek Medical Center and The Hebrew University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Varda","middleName":"","lastName":"Gross-Tsur","suffix":""}],"badges":[],"createdAt":"2025-02-19 13:23:09","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6064456/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6064456/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41598-025-98666-w","type":"published","date":"2025-04-17T15:57:13+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":81050950,"identity":"90b49dce-a773-4d37-aacc-ec8bb90bb191","added_by":"auto","created_at":"2025-04-21 16:08:23","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":315838,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6064456/v1/cec9b5c3-0125-4db3-958e-62395fc79576.pdf"},{"id":79259236,"identity":"428a70d0-7cfd-48b7-ad43-07d3981b5747","added_by":"auto","created_at":"2025-03-26 09:18:25","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":11660,"visible":true,"origin":"","legend":"","description":"","filename":"heightlossinPWStable1.docx","url":"https://assets-eu.researchsquare.com/files/rs-6064456/v1/29c6044d91055ebd8a0b8513.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Height loss with age in adults with Prader-Willi syndrome may result in artifactual increases in BMI","fulltext":[{"header":"Introduction","content":"\u003cp\u003eBody mass index (BMI) [weight in kg/(height in m)\u003csup\u003e2\u003c/sup\u003e] is the most commonly used measure of obesity in children and adults. BMI values classify adults as overweight (≥ 25.0 to 29.9kg/m\u003csup\u003e2\u003c/sup\u003e), obesity class I (30.0–34.9 kg/m\u003csup\u003e2\u003c/sup\u003e), obesity class II (35.0–39.9 kg/m\u003csup\u003e2\u003c/sup\u003e), or obesity class III (≥ 40kg/m\u003csup\u003e2\u003c/sup\u003e)[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Prader-Willi syndrome (PWS) results from deletion or lack of expression of specific genes on the paternal chromosome 15 and is associated with severe obesity due to lack of satiety and severe hyperphagia [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Individuals with PWS require strict control of diet and exercise in order to prevent weight gain and complications of morbid obesity. For these patients, even minor changes in BMI, may lead to recommendations for either increasing or decreasing daily caloric intake and/or changes in exercise regimens in order to prevent excessive weight gain.\u003c/p\u003e \u003cp\u003eNormal aging is usually associated with modest decreases in standing height and has only a minimal effect on BMI values [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Height loss may result from vertebral fractures, disc collapse, or kyphoscoliosis. Accurate measurements of standing heights in adults with PWS are sometimes difficult to attain due to the high prevalence of kyphoscoliosis, hypotonia and poor posture in this population [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e–\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. An apparent decrease in height measurements will result in an increased BMI value, even when the person's weight has not changed.\u003c/p\u003e "},{"header":"Methods and study population","content":"\u003cp\u003eWe studied, retrospectively, all 28 adults (mean age 35.9 ± 5.3 years at the latest follow-up visit) with genetically confirmed PWS who were followed in our multidisciplinary national PWS clinic for at least five years after the age of 20 years. Standing height was measured by a trained clinic assistant using a\u003c/p\u003e\u003cp\u003ewall-mounted stadiometer. Patients were measured without shoes and weighed in light clothing. If the measured height differed by more than 1 cm, the height measurement was repeated by a pediatric endocrinologist (HJH). We compared the tallest height (H-1) recorded after age 20 years (mean age 24.7 ± 3.6 years) with the height (H-2) at the latest clinic visit (mean age 35.9 ± 5.3 years). Mean duration of follow-up was 11.3 ± 3.4 (range 5.1 to 16.2) years.\u003c/p\u003e\u003cp\u003e Written informed consent was obtained from study participants and parents or guardians as part of an ongoing study of growth and development which was approved by the institutional review board of the Shaare Zedek Medical Center, Jerusalem. All study protocols were carried out in accordance with relevant guidelines and regulations. The datasets used and analysed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eThree individuals had no loss of height and seven had a slight gain in height (mean gain 1.6 cm, range 0.5\u0026ndash;2.7 cm). Fourteen patients had mild height loss (H-2 minus H-1) of 1.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.8 cm over a duration of 10.9\u0026thinsp;\u0026plusmn;\u0026thinsp;3.8 years. Standing height measurements for four patients consistently decreased at yearly visits and at a mean age of 35.6\u0026thinsp;\u0026plusmn;\u0026thinsp;5.5 years were significantly shorter than the measured heights at age 23.1\u0026thinsp;\u0026plusmn;\u0026thinsp;3.3 years (Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). BMI values using the latest measured heights (H-2) were increased compared to the values calculated by using their \u0026ldquo;true\u0026rdquo; heights (H-1) by 3.8, 2.8, 2.5, and 2.4 kg/m2, respectively and as shown in Table \u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBMI values for four individuals with Prader-Willi syndrome and height loss\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePt. 1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePt. 2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePt. 3\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePt. 4\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years)at latest measurement\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e42.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e37.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e30.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePWS genotype\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eUPD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDEL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eDEL\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration of follow-up (yrs)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eH-1 (cm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e152.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e142.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e148.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e145.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eH-2 (cm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e145.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e136.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e141.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e139.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHeight loss (cm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-6.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-6.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-7.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-6.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI (kg/m2) for measured height\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e41.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e31.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e27.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI (kg/m2) for estimated \"true\" height\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e37.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e28.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e24.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eTable legend: BMI values for the four adults with PWS whose measured heights decreased significantly. PWS genotypes: IC, imprinting center defect; UPD, uniparental disomy; DEL, deletion. H-1 is the tallest height measured after age 20 years. H-2 is the height measured at the latest clinic visit. Height loss is the value of H-2 minus H-1. BMI (weight in kg/[height in m]\u003csup\u003e2\u003c/sup\u003e) values were calculated using the weight at the latest clinic visit, height at the latest clinic visit (H-2), and then recalculated assuming \"true\" height (H-1) .\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eWe reviewed the medical records of these four patients, who are at the highest risk for a potential increase of BMI value, even without any weight gain, and to try to understand why they underwent a greater loss of height compared to the overall group.\u003c/p\u003e \u003cp\u003eOn x-ray examination at age 41 years, patient #1 had compression fractures seen in vertebrae L-1 to L-5. Although patient #2 had severe kyphosis, he underwent fusion of nine or more vertebrae and vertebral osteotomy which would have been expected to increase his height. Patient #3 had osteoporosis (Z-score for lumbar spine was \u0026minus;\u0026thinsp;3.2) but did not have documented vertebral fractures. At age 27 years, x-rays of patient #4 showed scoliosis of 41 degrees and kyphosis of 40 degrees.\u003c/p\u003e \u003cp\u003eBMI values calculated according to the latest measured heights were significantly higher than the BMI values determined using H-1 measurements as the assumed \"true\" heights, as shown in table one. After adjusting BMI values to compensate for height loss, patient #1 was reclassified as obesity class II vs obesity class III, two patients were reclassified as being people with overweight instead of being people with obesity, and the reduced BMI value for patient 4 was in the borderline normal range.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe causes of severe height loss in adults with PWS are most likely multifactorial and may not always be attributed to a specific orthopedic diagnosis. Nevertheless, the consistent decrease in measured heights in four individuals resulted in higher values of BMI for the same weight compared to BMI values using their \"true\" height for the calculation. Accurate measurements of standing height may be difficult in some individuals with PWS due to hypotonia, kyphoscoliosis, and poor posture. Nevertheless, for most adults followed in our clinic, recorded heights were stable with minimal or no height loss over five to 16 years of follow-up. Therefore, the consistent and gradual decrease in measured heights for the four individuals with significant height loss cannot be attributed to improper measuring technique.\u003c/p\u003e \u003cp\u003eSorkin et al described cumulative height losses of approximately 5 cm for men and 6 cm for women from young adulthood to\"old age,\" based on three epidemiologic population studies (7). The impact of height loss on increasing BMI was relatively small, however, in the range of 1.5 kg/m\u003csup\u003e2\u003c/sup\u003e. In contrast to a general population, even minor increases in BMI are significant for individuals with PWS.\u003c/p\u003e \u003cp\u003eThe apparent increase in BMI due to height loss rather than due to weight gain, may lead to inappropriate recommendations for caloric intake and exercise regimens. Some guidelines for individuals with PWS use height as one of the criteria for prescribing the recommended daily caloric intake: 10\u0026ndash;14 kcal/cm of height for weight maintenance and 7\u0026ndash;8 kcal/cm of height for weight loss [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. In our group homes dedicated specifically for individuals with PWS, typical diets provide 1400 kcal/day for weight maintenance. When weight and/or BMI increases, caloric intake is reduced to 1200 kcal/day.\u003c/p\u003e \u003cp\u003eRecognition of the effect of height loss in aging is important for individual nutritional guidance in order to avoid unnecessary reduction in caloric intake. In our multidisciplinary PWS clinic, we follow our patients from adolescence through adulthood, including yearly height measurements. Therefore, we were able to recognize that the apparent increase in BMI in these four individuals was due to height loss and not to excessive weight gain.\u003c/p\u003e \u003cp\u003eFor individuals with Prader-Willi Syndrome, even minor dietary changes, can significantly affect their mood and behavior. For example, we describe two patients with PWS who gained weight and whose BMI truly increased, not due to height loss, who displayed strong emotional responses when they were told to decrease their caloric intake. During a routine visit in our multidisciplinary PWS clinic, a 43 year- old woman became very distressed when told that she had gained weight. When recommendations to reduce caloric intake were discussed, she became very upset, started crying, and abruptly ran out of the room, slamming the door. She stood outside, shouted, and refused to participate in any further discussion or examinations.\u003c/p\u003e \u003cp\u003eWhen a 26-year-old man with PWS was told by his dietitian that he needed to reduce his caloric intake by 100 kcal/day because of weight gain, he became very agitated. He started cursing, physically threatened the dietitian and broke his own glasses.\u003c/p\u003e \u003cp\u003eIn conclusion, recognizing the impact of height loss on BMI is essential for providing appropriate nutritional guidance and avoiding unnecessary reductions in caloric intake. Records of previous height measurements should be made available especially when individuals with PWS are transitioned from pediatric or adolescent centers to adult clinic settings. Additionally, attention to the impact of height loss on BMI may be important for research studies evaluating the effects of lifestyle changes and medical interventions for obesity, not only for individuals with PWS.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eH.J.H. collected and analyzed the patient data, wrote the main manuscript; H.A. provided orthopedic consultations and reviewed the manuscript; F.B. reviewed and recommended revisions of the manuscript; V.G.T. collected patient data, contributed to writing and reviewing the manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eWe wish to thank Miriam Attia for organizing and collecting data from the medical records and Dorit Forer, clinical dietitian, for sharing her experience with providing nutritional guidance to our patients with PWS.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe datasets used and analysed during the current study are available from the corresponding author upon reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eFryar, C. D., Carroll, M. D. \u0026amp; Afful, J. \u003cem\u003ePrevalence of overweight, obesity, and severe obesity among adults aged 20 and over: United States, 1960\u0026ndash;1962 through 2017\u0026ndash;2018\u003c/em\u003e (NCHS Health E-Stats, 2020).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAngulo, M. A., Butler, M. G. \u0026amp; Cataletto, M. E. Prader-Willi syndrome: a review of clinical, genetic, and endocrine findings. \u003cem\u003eJ. Endocrinol. Invest.\u003c/em\u003e \u003cb\u003e38\u003c/b\u003e (12), 1249\u0026ndash;1263. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s40618-015-0312-9\u003c/span\u003e\u003cspan address=\"10.1007/s40618-015-0312-9\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2015). Epub 2015 Jun 11.PMID: 26062517.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSorkin, J. D., Muller, D. C. \u0026amp; Andres, R. Longitudinal change in height of men and women: implications for interpretation of the body mass index: the Baltimore Longitudinal Study of Aging. Am J Epidemiol. ;150(9):969\u0026thinsp;\u0026ndash;\u0026thinsp;77. (1999). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/oxfordjournals.aje.a010106\u003c/span\u003e\u003cspan address=\"10.1093/oxfordjournals.aje.a010106\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. PMID: 10547143.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCrin\u0026ograve;, A. et al. High Prevalence of Scoliosis in a Large Cohort of Patients with Prader-Willi Syndrome. \u003cem\u003eJ. Clin. Med.\u003c/em\u003e \u003cb\u003e11\u003c/b\u003e (6), 1574. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/jcm11061574\u003c/span\u003e\u003cspan address=\"10.3390/jcm11061574\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2022).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003evan Bosse, H. J. P. \u0026amp; Butler, M. G. Clinical Observations and Treatment Approaches for Scoliosis in Prader-Willi Syndrome. \u003cem\u003eGenes (Basel)\u003c/em\u003e. \u003cb\u003e11\u003c/b\u003e (3), 260. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3390/genes11030260\u003c/span\u003e\u003cspan address=\"10.3390/genes11030260\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2020).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHoffman, C. J., Aultman, D. \u0026amp; Pipes, P. A nutrition survey of and recommendations for individuals with Prader-Willi syndrome who live in group homes. \u003cem\u003eJ. Am. Diet. Assoc.\u003c/em\u003e \u003cb\u003e92\u003c/b\u003e (7), 823\u0026ndash;830 (1992). 833.PMID: 1624651.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSorkin, J. D., Muller, D. C. \u0026amp; Andres, R. Longitudinal Change in the Heights of Men and Women: Consequential Effects on Body Mass Index. \u003cem\u003eEpidemiol. Rev.\u003c/em\u003e \u003cb\u003e21\u003c/b\u003e (2), 247\u0026ndash;260. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/oxfordjournals.epirev.a018000\u003c/span\u003e\u003cspan address=\"10.1093/oxfordjournals.epirev.a018000\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (1999).\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-6064456/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6064456/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eModest decreases in height occur during normal aging, but usually have only a minimal effect on BMI (body mass index). Height loss may result from vertebral fractures, disc collapse, kyphosis, and/or scoliosis. Accurate determinations of BMI values are essential for prescribing diet and exercise regimens especially for adults with Prader-Willi syndrome (PWS). We measured standing heights in 28 PWS adults over a duration 11.3\u0026thinsp;\u0026plusmn;\u0026thinsp;3.4 (range 5.1 to 16.2) years in our national multidisciplinary PWS clinic. Most had no or only minimal height loss, but in four individuals measured heights decreased by 6.2, 6.6, 7.0, and 6.3 cm, respectively. Height loss for these four patients resulted in artifactually high BMI values compared to values based on heights measured 7.9 to 16.1 years earlier. The apparent increase in BMI due to height loss rather than weight gain may lead to inappropriate recommendations for reduction in caloric intake. Even minor changes in diet restrictions can affect mood and behavior in individuals with PWS. Recognition of height loss as a contributing factor to BMI calculations is important for clinical studies evaluating effects of life-style changes and medical interventions for obesity.\u003c/p\u003e","manuscriptTitle":"Height loss with age in adults with Prader-Willi syndrome may result in artifactual increases in BMI","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-03-26 09:10:21","doi":"10.21203/rs.3.rs-6064456/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Accepted","date":"2025-04-14T09:00:55+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-03-27T23:12:15+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"159980573226470351045623480197700068803","date":"2025-03-26T17:34:32+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-03-25T10:28:35+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-03-24T05:15:03+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2025-03-21T09:58:28+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"e3062685-6211-46b9-98ae-76c5e129ef07","owner":[],"postedDate":"March 26th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":46178595,"name":"Health sciences/Diseases"},{"id":46178596,"name":"Health sciences/Diseases/Metabolic disorders"},{"id":46178597,"name":"Biological sciences/Genetics/Clinical genetics"}],"tags":[],"updatedAt":"2025-04-21T16:02:48+00:00","versionOfRecord":{"articleIdentity":"rs-6064456","link":"https://doi.org/10.1038/s41598-025-98666-w","journal":{"identity":"scientific-reports","isVorOnly":false,"title":"Scientific Reports"},"publishedOn":"2025-04-17 15:57:13","publishedOnDateReadable":"April 17th, 2025"},"versionCreatedAt":"2025-03-26 09:10:21","video":"","vorDoi":"10.1038/s41598-025-98666-w","vorDoiUrl":"https://doi.org/10.1038/s41598-025-98666-w","workflowStages":[]},"version":"v1","identity":"rs-6064456","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6064456","identity":"rs-6064456","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}