Multicenter Study

. 2022 Dec 17;108(1):59-84.

doi: 10.1210/clinem/dgac556.

Bone Health in Adults With Prader-Willi Syndrome: Clinical Recommendations Based on a Multicenter Cohort Study

Denise H van Abswoude^{1

2

3

4}, Karlijn Pellikaan^{1

2

3

4}, Anna G W Rosenberg^{1

2

3

4}, Kirsten Davidse^{1

2

3

4}, Muriel Coupaye^{5

6}, Charlotte Høybye^{6

7

8

9}, Tania P Markovic^{6

10

11}, Graziano Grugni^{6

7

12}, Antonino Crinò^{6

13}, Assumpta Caixàs^{6

14

15}, Christine Poitou^{5

6

7}, Helena Mosbah⁵, Tessa Weir^{16

17}, Leo A van Vlimmeren¹⁸, Joost P H J Rutges¹⁹, Luuk W L De Klerk²⁰, M Carola Zillikens^{1

7

21

22}, Aart J van der Lely¹, Laura C G de Graaff^{1

2

3

4

6

7}

Affiliations

¹ Department of Internal Medicine, Division of Endocrinology, Erasmus Medical Center, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands.
² Center for Adults with Rare Genetic Syndromes, Department of Internal Medicine, Division of Endocrinology, Erasmus Medical Center, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands.
³ Dutch Center of Reference for Prader-Willi Syndrome, 3015 GD Rotterdam, The Netherlands.
⁴ Academic Center for Growth Disorders, Erasmus Medical Center, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands.
⁵ Assistance Publique-Hôpitaux de Paris, Rare Diseases Center of reference 'Prader-Willi Syndrome and obesity with eating disorders' (PRADORT), Nutrition Department, Institute of Cardiometabolism and Nutrition, ICAN, Pitié-Salpêtrière Hospital, Sorbonne Université, INSERM, Nutriomics, F75013 Paris, France.
⁶ International Network for Research, Management & Education on adults with Prader-Willi Syndrome (INfoRMEd-PWS).
⁷ ENDO-ERN (European Reference Network).
⁸ Department of Molecular Medicine and Surgery, Karolinska Institute and Karolinska University Hospital, Stockholm, Sweden.
⁹ Department of Endocrinology, Karolinska Institute and Karolinska University Hospital, Stockholm, Sweden.
¹⁰ Metabolism & Obesity Services, Royal Prince Alfred Hospital, Camperdown, Australia.
¹¹ Boden Initiative, Charles Perkins Centre, University of Sydney, SydneyAustralia.
¹² Divison of Auxology, Istituto Auxologico Italiano, IRCCS, Piancavallo (VB), Italy.
¹³ Reference Center for Prader-Willi syndrome, Bambino Gesù Hospital, Research Institute, Palidoro (Rome), Italy.
¹⁴ Department of Endocrinology and Nutrition, Hospital Universitari Parc Taulí, Institut d'Investigació i Innovació Parc Taulí (I3PT), Universitat Autònoma de Barcelona, Sabadell, Spain.
¹⁵ Department of Medicine, Universitat Autònoma de Barcelona, Sabadell, Spain.
¹⁶ Department of Endocrinology, Nepean-Blue Mountains Hospital, Sydney, NSW, Australia.
¹⁷ Northern Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia.
¹⁸ Department of Rehabilitation and Pediatric Physical Therapy, Radboud University Medical Centrum, 6525 GA Nijmegen, The Netherlands.
¹⁹ Department of Orthopedic surgery, Erasmus Medical Center, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands.
²⁰ Department of Orthopedic surgery, Sint Maartensclinic, 6500 GM Nijmegen, The Netherlands.
²¹ Academic Center for Rare Bone Disorders, Erasmus Medical Center, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands.
²² European Reference Network for rare bone diseases (ERN BOND).

PMID: 36149817
PMCID: PMC9759176
DOI: 10.1210/clinem/dgac556

Multicenter Study

Bone Health in Adults With Prader-Willi Syndrome: Clinical Recommendations Based on a Multicenter Cohort Study

Denise H van Abswoude et al. J Clin Endocrinol Metab. 2022.

. 2022 Dec 17;108(1):59-84.

doi: 10.1210/clinem/dgac556.

Authors

Affiliations

¹ Department of Internal Medicine, Division of Endocrinology, Erasmus Medical Center, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands.
² Center for Adults with Rare Genetic Syndromes, Department of Internal Medicine, Division of Endocrinology, Erasmus Medical Center, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands.
³ Dutch Center of Reference for Prader-Willi Syndrome, 3015 GD Rotterdam, The Netherlands.
⁴ Academic Center for Growth Disorders, Erasmus Medical Center, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands.
⁵ Assistance Publique-Hôpitaux de Paris, Rare Diseases Center of reference 'Prader-Willi Syndrome and obesity with eating disorders' (PRADORT), Nutrition Department, Institute of Cardiometabolism and Nutrition, ICAN, Pitié-Salpêtrière Hospital, Sorbonne Université, INSERM, Nutriomics, F75013 Paris, France.
⁶ International Network for Research, Management & Education on adults with Prader-Willi Syndrome (INfoRMEd-PWS).
⁷ ENDO-ERN (European Reference Network).
⁸ Department of Molecular Medicine and Surgery, Karolinska Institute and Karolinska University Hospital, Stockholm, Sweden.
⁹ Department of Endocrinology, Karolinska Institute and Karolinska University Hospital, Stockholm, Sweden.
¹⁰ Metabolism & Obesity Services, Royal Prince Alfred Hospital, Camperdown, Australia.
¹¹ Boden Initiative, Charles Perkins Centre, University of Sydney, SydneyAustralia.
¹² Divison of Auxology, Istituto Auxologico Italiano, IRCCS, Piancavallo (VB), Italy.
¹³ Reference Center for Prader-Willi syndrome, Bambino Gesù Hospital, Research Institute, Palidoro (Rome), Italy.
¹⁴ Department of Endocrinology and Nutrition, Hospital Universitari Parc Taulí, Institut d'Investigació i Innovació Parc Taulí (I3PT), Universitat Autònoma de Barcelona, Sabadell, Spain.
¹⁵ Department of Medicine, Universitat Autònoma de Barcelona, Sabadell, Spain.
¹⁶ Department of Endocrinology, Nepean-Blue Mountains Hospital, Sydney, NSW, Australia.
¹⁷ Northern Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia.
¹⁸ Department of Rehabilitation and Pediatric Physical Therapy, Radboud University Medical Centrum, 6525 GA Nijmegen, The Netherlands.
¹⁹ Department of Orthopedic surgery, Erasmus Medical Center, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands.
²⁰ Department of Orthopedic surgery, Sint Maartensclinic, 6500 GM Nijmegen, The Netherlands.
²¹ Academic Center for Rare Bone Disorders, Erasmus Medical Center, University Medical Center Rotterdam, 3015 GD Rotterdam, The Netherlands.
²² European Reference Network for rare bone diseases (ERN BOND).

PMID: 36149817
PMCID: PMC9759176
DOI: 10.1210/clinem/dgac556

Erratum in

Correction to "Bone health in adults with Prader-Willi syndrome: clinical recommendations based on a multicenter cohort study".
[No authors listed] [No authors listed] J Clin Endocrinol Metab. 2023 Jan 17;108(2):e30. doi: 10.1210/clinem/dgac680. J Clin Endocrinol Metab. 2023. PMID: 36451552 Free PMC article. No abstract available.

Abstract

Context: Prader-Willi syndrome (PWS) is a rare complex genetic syndrome, characterized by delayed psychomotor development, hypotonia, and hyperphagia. Hormone deficiencies such as hypogonadism, hypothyroidism, and growth hormone deficiency are common. The combination of hypotonia, low physical activity, and hypogonadism might lead to a decrease in bone mass and increase in fracture risk. Moreover, one would expect an increased risk of scoliosis due to hypotonia and low physical activity.

Objective: To study the prevalence and risk factors for skeletal problems (reduced bone mineral density, fractures, and scoliosis) in adults with PWS.

Methods: We retrospectively collected patient characteristics, medical history, medication, biochemical measurements, dual-energy X-ray absorptiometry scans, and spinal X-rays and reviewed the current literature.

Results: We included 354 adults with PWS (median age 31 years; 43% males), of whom 51 (14%) had osteoporosis (T-score below -2.5) and 143 (54%) had osteopenia (T-score -1 to -2.5). The most prevalent modifiable risk factors for osteoporosis were hypogonadism, insufficient dairy intake, sedentary lifestyle, and corticosteroid use. Male sex was associated with osteoporosis (P = .005). Growth hormone treatment was not associated with osteoporosis. A history of vertebral fractures was present in 10 (3%) and nonvertebral fractures in 59 (17%). Scoliosis was present in 263 (80%), but no modifiable risk factors were identified.

Conclusion: Besides scoliosis, osteoporosis is common in adults with PWS. Based on the literature and the risk factors for osteoporosis found in our cohort, we provide practical clinical recommendations to avoid skeletal complications in these vulnerable patients.

Keywords: Prader–Willi syndrome; bone density; hormone replacement therapy; human growth hormone; osteoporosis; scoliosis.

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Conflict of interest statement

Conflict of Interest The authors have no conflict of interest to disclose.

Figures

**Figure 1.**
Recommendations for the prevention, detection, and treatment of osteoporosis in adults with PWS (49, 95, 96). Abbreviations: DXA, dual-energy X-ray absorptiometry; PWS, Prader–Willi syndrome; VFA, vertebral fracture assessment.

**Figure 2.**
Recommendations for the detection, monitoring of progression, and treatment of scoliosis in adults with PWS (97–99). Abbreviation: GHt, growth hormone therapy.

See this image and copyright information in PMC

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Bone Health in Adults With Prader-Willi Syndrome: Clinical Recommendations Based on a Multicenter Cohort Study

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Bone Health in Adults With Prader-Willi Syndrome: Clinical Recommendations Based on a Multicenter Cohort Study

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