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

Abstract

Context Prader-Willi syndrome (PWS) is a rare complex genetic syndrome, characterized by delayed psychomotor development, hypotonia and hyperphagia. Hormone deficiencies like 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 (DEXA) 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= 0.005). Growth hormone treatment was not associated with osteoporosis. A history of vertebral fractures was present in 10 (3%) and non-vertebral 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.

A questionnaire-based survey of medical conditions in adults with Prader-Willi syndrome in Japan: implications for transitional care

“…Medical conditions and the efficacy of transitional care in adults with PWS have been examined in detail overseas. van [20]. Comorbidities with a high prevalence include T2DM, sleep abnormalities, scoliosis, and a low bone mineral density [20][21][22][23], and mortality rates were shown to be higher in patients with PWS than in a reference population [24].…”

“…van [20]. Comorbidities with a high prevalence include T2DM, sleep abnormalities, scoliosis, and a low bone mineral density [20][21][22][23], and mortality rates were shown to be higher in patients with PWS than in a reference population [24]. The efficacy of GH therapy during childhood to reduce mortality has been demonstrated.…”

“…Eleven subjects did not provide information on sex (Table 1). The median age of patients was 14 years (IQR: [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] and ranged between 0 and 48 years (Fig. 1A), with 162 subjects being equal to or older than 18 years, who were hereafter referred to as adult patients.…”

“…SSRT was administered to 26.6 and 19.5% of male and female adult patients, respectively, which is considered to be low based on the high prevalence of hypogonadism in PWS patients, particularly in males [21,[36][37][38]. The low rate of SSRT may be characteristic to Japan because SSRT was administered to the majority of adult PWS patients with hypogonadism according to publications overseas [15,20]. This is in part because guardians expressed concerns regarding the deterioration of psychological and behavioral symptoms after the initiation of SSRT; however, there is currently no information on the unfavorable influence of SSRT on psychological and behavioral conditions in PWS.…”

“…Multiple reviews have indicated that a gradual increase in SSRT is tolerated well by adolescents with PWS [2,39]. Since impaired skeletal health, including low bone mineral density, is prevalent in PWS [20] and is mainly caused by inappropriate SSRT, SSRT needs to be considered where appropriate. Moreover, the introduction of SSRT is supported by findings showing that SSRT increased the lean body mass and reduced the fat mass in male patients with PWS [40].…”