Background
Cohorts of childhood acute lymphoblastic leukemia (cALL) survivors reaching adulthood are increasing. Approximately 30% of survivors meet criteria for low bone mineral density (BMD) ...10 years after diagnosis. We investigated risk factors for low BMD in long‐term cALL survivors.
Methods
We recruited 245 cALL survivors from the PETALE (Prévenir les effets tardifs des traitements de la leucémie aiguë lymphoblastique chez l'enfant) cohort, who were treated with the Dana Farber Cancer Institute protocols, did not experience disease relapse or hematopoietic stem cell transplants, and presented with more than 5 years of event‐free survival. Median time since diagnosis was 15.1 years.
Results
Prevalence of low DXA‐derived BMD (Z‐score ≤−1) ranged between 21.9% and 25.3%, depending on site (lumbar spine (LS‐BMD), femoral neck (FN‐BMD), and total body (TB‐BMD), and between 3.7% and 5.8% for very low BMD (Z‐score ≤−2). Males had a higher prevalence of low BMD than females for all three outcomes (26%–32% vs. 18%–21%), and male sex acted as a significant risk factor for low BMD in all models. Treatment‐related factors such as cumulative glucocorticoid (GC) doses and cranial radiation therapy (CRT) were associated with lower BMDs in the full cohort and in females at the FN‐BMD site.
Conclusion
Low and very low BMD is more prevalent in male cALL survivors. Male sex, high cumulative GC doses, CRT, risk group, and low body mass index (BMI) were identified as risk factors for low BMD. A longer follow‐up of BMD through time in these survivors is needed to establish if low BMD will translate into a higher risk for fragility fractures through adulthood.
Osteogenesis imperfecta (OI) is a rare genetic disorder of the bones caused by a mutation in Type I collagen genes. As adults with OI are aging, medical concerns secondary to OI may arise. This ...integrative review sought to review, appraise, and synthesize the clinical manifestations faced by adults with OI. Four electronic bibliographic databases were searched. Published quantitative, qualitative, and mixed‐methods studies, as well as case reports from 2000 to March 2019, addressing a clinical manifestation in adulthood, were reviewed. Eligible studies and case reports were subsequently appraised using the Mixed Methods Appraisal Tool and Case Report Checklist, respectively. Twenty quantitative studies and 88 case reports were included for review regardless of the varying methodological quality score. These studies collectively included 2,510 adults with different OI types. Several clinical manifestations were studied, and included: hearing loss, cardiac diseases, pregnancy complications, cerebrovascular manifestations, musculoskeletal manifestations, respiratory manifestations, vision impairment, and other clinical manifestations. Increased awareness may optimize prevention, treatment, and follow‐up. Opportunities to enhance the methodological quality of research including better design and methodology, multisite collaborations, and larger and diverse sampling will optimize the generalizability and transferability of findings.
Arthrogryposis multiplex congenita (AMC) is characterized by congenital joint contractures present in two or more body areas. Lack of fetal movement is the underlying cause of AMC, which can lead to ...abnormal connective tissue surrounding the joint resulting in stiffness and muscle atrophy. Treatment aims at improving function and mobility through surgical and/or conservative interventions. A scoping review was conducted to explore the existing knowledge of the evaluation and treatment of muscle and joint function in children with AMC. Three search engines were included and identified 1,271 articles. Eighty‐seven studies met the selection criteria and were included in this review. All included studies focused on joints, 30 of which also assessed the muscle. Assessment most often included the position of the contractures (n = 72), as well as range of motion (n = 66). Interventions to improve muscle and joint function were reported in 82 of the 87 papers and included surgery (n = 70) and conservative interventions (n = 74) with bony surgery (i.e., osteotomy) the most common surgery and rehabilitation the most common conservative intervention. Recurrences of contractures were mentioned in 46 of the 68 studies providing a follow‐up. Future studies should use validated measures to assess muscle and joint function, and conservative interventions should be described in greater detail and to include a longer follow‐up.
Knee kinematics during a drop vertical jump, measured by the Kinect V2 (Microsoft, Redmond, WA, USA), have been shown to be associated with an increased risk of non-contact anterior cruciate ligament ...injury. The accuracy and reliability of the Microsoft Kinect V2 has yet to be assessed specifically for tracking the coronal and sagittal knee angles of the drop vertical jump. Eleven participants performed three drop vertical jumps that were recorded using both the Kinect V2 and a gold standard motion analysis system (Vicon, Los Angeles, CA, USA). The initial coronal, peak coronal, and peak sagittal angles of the left and right knees were measured by both systems simultaneously. Analysis of the data obtained by the Kinect V2 was performed by our software. The differences in the mean knee angles measured by the Kinect V2 and the Vicon system were non-significant for all parameters except for the peak sagittal angle of the right leg with a difference of 7.74 degrees and a
-value of 0.008. There was excellent agreement between the Kinect V2 and the Vicon system, with intraclass correlation coefficients consistently over 0.75 for all knee angles measured. Visual analysis revealed a moderate frame-to-frame variability for coronal angles measured by the Kinect V2. The Kinect V2 can be used to capture knee coronal and sagittal angles with sufficient accuracy during a drop vertical jump, suggesting that a Kinect-based portable motion analysis system is suitable to screen individuals for the risk of non-contact anterior cruciate ligament injury.
Purpose
Here, we review the skeletal effects of pediatric muscle disorders as well as muscle impairment in pediatric bone disorders.
Recent Findings
When starting in utero, muscle disorders can lead ...to congenital multiple contractures. Pediatric-onset muscle weakness such as cerebral palsy, Duchenne muscular dystrophy, spinal muscular atrophy, or spina bifida typically are associated with small diameter of long-bone shafts, low density of metaphyseal bone, and increased fracture incidence in the lower extremities, in particular, the distal femur. Primary bone diseases can affect muscles through generic mechanisms, such as decreased physical activity or in disease-specific ways. For example, the collagen defect underlying the bone fragility of osteogenesis imperfecta may also affect muscle force generation or transmission. Transforming growth factor beta released from bone in Camurati Engelman disease may decrease muscle function.
Future Directions
Considering muscle-bone interactions does not only contribute to the understanding of musculoskeletal disorders but also can identify new targets for therapeutic interventions.
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.
Context:
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.
Objective:
Our ...objective was to assess calf muscle size and density (an indicator of muscle quality) and lower extremity muscle function in patients with HPR.
Setting:
The study was carried out in the outpatient department of a pediatric orthopedic hospital.
Patients and Other Participants:
Participants included 34 individuals with HPR (6–60 yr; nine males) and 34 age- and gender-matched controls.
Main Outcome Measures:
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.
Results:
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.
Conclusions:
The present study suggests that muscle weakness is a clinical feature of HPR. Lower muscle quality and limb deformities contribute to this functional deficit.
Heterozygous mutations in the gene encoding the sphingomyelin synthase 2, SGMS2, have recently been linked to childhood-onset osteoporosis and skeletal dysplasia. One nonsense variant at position ...c.148C>T (p.Arg50*) has been associated with mild bone fragility with or without cranial sclerosis. Here we assessed the effect of the SGMS2 p.Arg50* variant in two unrelated probands with childhood-onset osteoporosis and their unaffected family members. We found that the p.Arg50* variant was associated with phenotypic variability, ranging from absence of a bone phenotype to severe vertebral compression fractures and low lumbar spine areal bone mineral density (BMD) as measured by dual energy x-ray absorptiometry. Peripheral quantitative computed tomography of the radius and tibia in the two probands revealed low cortical volumetric BMD and reduced cortical thickness. In addition, both probands were obese and suffered from muscle function deficits compared to sex- and age-matched controls. Long-term bisphosphonate treatment was associated with reshaping of previously compressed vertebral bodies.
•SMGS2-associated osteoporosis resembles osteogenesis imperfecta.•The SGMS2 p.Arg50* variant is associated with bone fragility with incomplete penetrance.•Cortical bone is thin and porous in SGMS2-associated osteoporosis.•Bisphosphonates seem to be effective at treating SGMS2-associated osteoporosis.
Acute Lymphoblastic Leukemia (ALL) is the most common pediatric cancer. ALL and its treatment cause altered bone-mineral homeostasis, which can contribute to musculoskeletal late adverse effects ...(LAEs). With the increasing number of childhood cancer survivors, LAEs are reported often, and are aggravated by inactive lifestyles. A telerehabilitation program is proposed to strengthen the muscle-bone complex and prevent future impairment.
This study aimed to explore and better understand patient and parent experience of a telerehabilitation program after completion of ALL treatment.
ALL survivors (
= 12), 75% girls, 7.9 to 14.7 years old, within six months to five years of treatment, were recruited to participate in the proposed study, along with a parent. The 16-week group program included 40 potential home-based physical activities, with monthly progression, supervised by a kinesiologist, through an online telerehabilitation platform. Patients could be included in the study if they joined during the first month of intervention of their group (minimum 12 weeks of intervention). A semi-structured post-intervention interview was conducted with the patients and their parent during the final assessment, along with a review of the kinesiologist's clinical notes, to obtain a portrait of the participants' experience with the telerehabilitation program. Overarching themes were identified by one author and confirmed by two senior authors before extracting the various aspects of each theme.
Of the 12 patients recruited, three were excluded from the analysis because they did not complete the minimum 12 weeks of intervention (one = relapse, one = failure to meet technical requirements, and one = abandoned due to parent's disinterest). The nine patients who completed the program (six girls; 10.93 ± 2.83 years) had a mean adherence of 89%. The overarching themes identified were the program modalities (group approach with patient-parent paired training, supervised by a kinesiologist), the telerehabilitation system, the participants' perception of the benefits, and recommendations and suggestions from the families. Both patients and parents expressed very high satisfaction with the program and perceived benefits.
Participants appreciated the program and reported they would all recommend it to other families in similar situations. The telerehabilitation method of service delivery was perceived by some as decisive in choosing to participate, while the supervision and intra- and inter-family interactions were the motivating factors that were key to program adherence.
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