Animal studies suggest that hypophosphatemic rickets (HPR) is associated with muscle function deficits, but it is unknown whether humans with HPR have a muscle disorder. Our objective was to assess calf muscle size and density (an indicator of muscle quality) and lower extremity muscle function in patients with HPR. The study was carried out in the outpatient department of a pediatric orthopedic hospital. Participants included 34 individuals with HPR (6-60 yr; nine males) and 34 age- and gender-matched controls. Calf muscle parameters (muscle cross-sectional area and density) were measured by peripheral quantitative computed tomography. Lower extremity muscle function (peak force per body weight and peak power per body mass) was measured by jumping mechanography through five tests with different levels of difficulty: multiple two-legged hopping, multiple one-legged hopping, single two-legged jump, chair-rise test, and heel-rise test. Compared with age- and gender-matched controls, patients with HPR had normal muscle size (P = 0.58) but lower muscle density (P = 0.008) and lower peak muscle force and power (P < 0.001 in each test). Muscle function tests were also lower in the subgroup of patients with straight legs (n = 13) than in controls, even though patients with straight legs had higher muscle function test results than patients with severe leg deformities. The present study suggests that muscle weakness is a clinical feature of HPR. Lower muscle quality and limb deformities contribute to this functional deficit.

Context: X-linked hypophosphatemic rickets is caused by mutations in PHEX. Even though the disease is characterized by disordered skeletal mineralization, detailed bone densitometric studies are lacking. Objective: The aim of the study was to assess volumetric bone mineral density (vBMD) in X-linked hypophosphatemic rickets using forearm peripheral quantitative computed tomography. Setting: The study was conducted in the metabolic bone clinic of a pediatric orthopedic hospital. Patients: Thirty-four patients (age, 6 to 60 years; 24 female) with PHEX mutations were studied, of whom 7 children (age, 6 to 11 years) were actively being treated with calcitriol and phosphate supplementation. Twenty-one patients (age, 16 to 40 years) had received the same therapy before but had discontinued the treatment; 6 patients (age, 12 to 60 years) had never received this treatment. Main Outcome Measures: Trabecular and cortical vBMD of the radius. Results: Trabecular vBMD was elevated (mean age-specific and sex-specific z-score: +1.0) when all patients were analyzed together, due to very high results in currently treated patients (mean z-score: +2.4) and slightly above-average mean values in the other patients. Cortical vBMD was low when the entire cohort was analyzed together (mean z-score: −3.3), but was higher in currently treated patients (mean z-score: −1.3) than in patients who had discontinued therapy (mean z-score: −3.8) or who had never been treated (mean z-score: −4.1). Conclusions: Patients with PHEX mutations have elevated trabecular vBMD at the distal radius while receiving calcitriol and phosphate supplementation, but low cortical vBMD at the radius diaphysis. Low cortical vBMD presumably reflects the underlying mineralization defect that is not entirely corrected by current treatment approaches.

Results of previous studies suggested that children and adolescents with osteogenesis imperfecta (OI) type I have a muscle force deficit. However, muscle function has only been assessed by static isometric force tests and not in more natural conditions such as dynamic force and power tests. The purpose of this study was to assess lower extremity dynamic muscle function and muscle anatomy in OI type I. The study was performed in the outpatient department of a pediatric orthopedic hospital. A total of 54 individuals with OI type I (6-21 years; 20 male) and 54 age- and sex-matched controls took part in this study. Calf muscle cross-sectional area and density were measured by peripheral quantitative computed tomography. Lower extremity muscle function (peak force per body weight and peak power per body mass) was measured by jumping mechanography through 5 tests: multiple two-legged hopping, multiple one-legged hopping, single two-legged jump, chair-rise test, and heel-rise test. Compared with age- and sex-matched controls, patients with OI type I had smaller muscle size (P = .04) but normal muscle density (P = .21). They also had lower average peak force and lower specific force (peak force/muscle cross-sectional area; all P < .008). Average peak power was lower in patients with OI type I but not significantly so (all P > .054). Children and adolescents with OI type I have, on average, a significant force deficit in the lower limb as measured by dynamic force tests. Nonetheless, these data also show that OI type I is compatible with normal muscle performance in some individuals.

Context: We recently found that patients with X-linked hypophosphatemic rickets (XLH) have a muscle function deficit in the lower extremities. As muscle force and bone mass are usually closely related, we hypothesized that patients with XLH could also have a bone mass deficit in the lower extremities. Objective: The study objective was to assess the muscle-bone relationship in the lower extremities of patients with XLH. Setting: The study was carried out in the outpatients department of a pediatric orthopedic hospital. Patients and Other Participants: Thirty individuals with XLH (6 to 60 y; 9 male patients) and 30 age- and gender-matched controls participated. Main Outcome Measures: Calf muscle size and density as well as tibia bone mass and geometry were assessed by peripheral quantitative computed tomography. Muscle function was evaluated as peak force in the multiple 2-legged hopping test. Results: Muscle force was significantly lower in XLH patients than in controls but muscle cross-sectional area did not differ (after adjustment for tibia length). External bone size, expressed as total bone cross-sectional area, was higher in the XLH group than in controls. The XLH cohort also had statistically significantly higher bone mineral content. Conclusions: Patients with XLH have increased bone mass and size at the distal tibia despite muscle function deficits.

Background: Acute lymphoblastic leukemia is the most common type of pediatric cancer. Acute lymphoblastic leukemia causes an altered bone mineral homeostasis state, which can contribute to osteopenia, and bone fractures, most commonly vertebral fractures. With the increasing number of childhood cancer survivors, late adverse effects such as musculoskeletal comorbidities are often reported and are further influenced by inactive lifestyle habits. Physical activity has been shown to increase the mechanical workload of the bone, mitigating bone impairment in other cancer-specific populations. Objective: This interventional pilot study aims to investigate the use of telehealth to deliver a home-based exercise intervention for early-on survivors of bone marrow–related hematological malignancies and to assess its impact on survivors’ musculoskeletal and functional health. Methods: We aimed to recruit a group of 12 early-on survivors of acute lymphoblastic leukemia, within 6 months to 5 years of treatment, to participate in and complete the proposed telehealth intervention with a parent. The 16-week intervention included 40 potential home-based physical activity interventions supervised by a kinesiologist through a telehealth internet platform, with monthly progression. Patients were recruited to the cohort if they were able to participate in the intervention during the first month (minimum 12 weeks of intervention). Evaluation before and after the intervention protocol highlighted differences in functional capacities and musculoskeletal health of patients using mechanography, peripheral quantitative computed tomography, 6-minute walk test, and grip force test. Results: The recruitment rate for the intervention was low (12/57, 21% of contacted patients). Of 12 patients, 3 were excluded (1=relapse, 1=failure to meet technical requirements, and 1=abandoned). The 9 patients who completed the intervention (6 girls; mean age 10.93, SD 2.83 years; mean BMI 21.58, SD 6.55 kg/m2; mean time since treatment completion 36.67, SD 16.37 months) had a mean adherence of 89% and a completion rate of 75%. In addition, these patients showed functional improvements in lower limb muscle force and power as well as in the 6-minute walk test distance. Participants also showed improved bone health after the intervention on the following parameters: bone mineral content, stress-strain index, total and cortical cross-sectional area at the 14% site (P=.03, P=.01, P=.01, and P=.001, respectively) and 38% site of the tibia (P=.003, P=.04, P=.001, and P=.003, respectively). Conclusions: High adherence and participation rates suggest that telehealth is a feasible method to deliver exercise interventions to young early-on survivors of acute lymphoblastic leukemia. The proposed intervention seems promising in providing benefits to patients’ functional performance and bone health, but a large-scale study is needed to confirm this assumption.