Low bone mineral density in achondroplasia and hypochondroplasia

Matsushita, Masaki; Kitoh, Hiroshi; Mishima, Kenichi; Kadono, Izumi; Sugiura, Hiroshi; Hasegawa, Sachi; Nishida, Yoshihiro; Ishiguro, Naoki

doi:10.1111/ped.12890

Cited by 21 publications

(18 citation statements)

References 22 publications

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“…Two small studies, of 10 and 11 adults, respectively, found reduced bone density measured by dual X‐ray absorptiometry …”

Section: Resultsmentioning

confidence: 99%

“…Interestingly, recent studies on mice have indicated that the FGFR3-mutation might protect from the development of arthritis in achondroplasia. 59 Two studies reported on osteopenia in achondroplasia, 17,19 but the studies are small and the findings need to be confirmed in future studies.…”

Section: Medical Complications Health Characteristics and Psychosomentioning

confidence: 96%

“…Brooks et al demonstrated a very low prevalence of anterior and posterior cruciate ligament injuries in 430 adults, indicating that anatomical differences may protect from this kind of injuries in achondroplasia 14. Two small studies, of 10 and 11 adults, respectively, found reduced bone density measured by dual X-ray absorptiometry 17,19.…”

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confidence: 99%

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Current knowledge of medical complications in adults with achondroplasia: A scoping review

et al. 2019

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This article provides an overview of the current knowledge on medical complications, health characteristics, and psychosocial issues in adults with achondroplasia. We have used a scoping review methodology particularly recommended for mapping and summarizing existing research evidence, and to identify knowledge gaps. The review process was conducted in accordance with the PRISMA-ScR guidelines (Preferred Reporting Items for Systematic reviews and Meta-Analyses Extension for Scoping Reviews). The selection of studies was based on criteria predefined in a review protocol. Twenty-nine publications were included; 2 reviews, and 27 primary studies. Key information such as reference details, study characteristics, topics of interest, main findings and the study author's conclusion are presented in text and tables. Over the past decades, there has only been a slight increase in publications on adults with achondroplasia. The reported morbidity rates and prevalence of medical complications are often based on a few studies where the methodology and representativeness can be questioned. Studies on sleep-related disorders and pregnancy-related complications were lacking. Multicenter natural history studies have recently been initiated. Future studies should report in accordance to methodological reference standards, to strengthen the reliability and generalizability of the findings, and to increase the relevance for implementing in clinical practice. K E Y W O R D S achondroplasia, adults, health-related quality of life, health status, medical complications, review

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“…Two small studies, of 10 and 11 adults, respectively, found reduced bone density measured by dual X‐ray absorptiometry …”

Section: Resultsmentioning

confidence: 99%

Section: Medical Complications Health Characteristics and Psychosomentioning

confidence: 96%

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Current knowledge of medical complications in adults with achondroplasia: A scoping review

et al. 2019

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“…6 demonstrated decreased bone mass in the metaphysis of the distal femur in Fgfr3 G369C/+ mice exhibiting gain-of-function in FGFR3 due to the elevated both osteoblastgenesis and osteoclastgenesis. Actually, bone mineral density was decreased in patients with human ACH 5 . The current study confirmed decreased trabecular bone in Fgfr3 ach mice by radiological and histological analyses.…”

Section: Discussionmentioning

confidence: 99%

“…Foramen magnum stenosis, hydrocephalus, and spinal canal stenosis are potentially serious complications of ACH 4 . In addition, osteoporotic features were also observed in patients with ACH 5 as well as in mouse model of ACH 6 . Histologically, FGFR3 is expressed in proliferative and prehypertrophic zones of the growth plate and modulates both proliferation and differentiation of the chondrocytes 7 .…”

Section: Introductionmentioning

confidence: 91%

Clinical dosage of meclozine promotes longitudinal bone growth, bone volume, and trabecular bone quality in transgenic mice with achondroplasia

Matsushita

Esaki

Mishima

et al. 2017

Sci Rep

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Achondroplasia (ACH) is the most common short-limbed skeletal dysplasia caused by gain-of-function mutations in the fibroblast growth factor receptor 3 (FGFR3). No effective FGFR3-targeted therapies for ACH are currently available. By drug repositioning strategies, we identified that meclozine, which has been used as an anti-motion-sickness, suppressed FGFR3 signaling in chondrocytes and rescued short-limbed phenotype in ACH mouse model. Here, we conducted various pharmacological tests for future clinical application in ACH. Pharmacokinetic analyses demonstrated that peak drug concentration (Cmax) and area under the concentration-time curve (AUC) of 2 mg/kg of meclozine to mice was lower than that of 25 mg/body to human, which is a clinical usage for anti-motion-sickness. Pharmacokinetic simulation studies showed that repeated dose of 2 mg/kg of meclozine showed no accumulation effects. Short stature phenotype in the transgenic mice was significantly rescued by twice-daily oral administration of 2 mg/kg/day of meclozine. In addition to stimulation of longitudinal bone growth, bone volume and metaphyseal trabecular bone quality were improved by meclozine treatment. We confirmed a preclinical proof of concept for applying meclozine for the treatment of short stature in ACH, although toxicity and adverse events associated with long-term administration of this drug should be examined.

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Medial patellar luxation in a chondrodysplastic Alaskan Malamute

Chong

Michelsen

2021

Vet Record Case Reports

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A 14‐month‐old Alaskan Malamute with chondrodysplasia (dwarfism) presented for progressive bilateral hindlimb lameness. A diagnosis of bilateral medially luxating patellae was made based on clinical and radiographic findings. The chondrodysplasia in this case was atypical in its hindlimb skeletal deformity along with atypical osteopaenia. The case was successfully managed with trochlear sulcoplasty and tibial tuberosity transposition; due to reduced bone quality, the tibial tuberosity was secured with a locking plate (ALPS; Kyon, Inc, Zurich, Switzerland). To the authors’ knowledge, treatment of patellar luxation in chondrodysplastic Alaskan Malamutes has not been previously reported.

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Low bone mineral density in achondroplasia and hypochondroplasia

Abstract: Spinal BMD was reduced in ACH/HCH patients, and was mildly correlated with individual BMI. We should carefully monitor BMD and examine osteoporosis-related symptoms in adolescent and adult ACH/HCH patients. © 2016 Japan Pediatric Society.

Cited by 21 publications

References 22 publications

Current knowledge of medical complications in adults with achondroplasia: A scoping review

Current knowledge of medical complications in adults with achondroplasia: A scoping review

Clinical dosage of meclozine promotes longitudinal bone growth, bone volume, and trabecular bone quality in transgenic mice with achondroplasia

Medial patellar luxation in a chondrodysplastic Alaskan Malamute

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