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Browsing by Author "van der Meulen, Marjolein C. H."
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Item In vivo axial loading of the mouse tibia(Springer, 2015) Melville, Katherine M.; Robling, Alexander G.; van der Meulen, Marjolein C. H.; Department of Anatomy and Cell Biology, IU School of MedicineNoninvasive methods to apply controlled, cyclic loads to the living skeleton are used as anabolic procedures to stimulate new bone formation in adults and enhance bone mass accrual in growing animals. These methods are also invaluable for understanding bone signaling pathways. Our focus here is on a particular loading model: in vivo axial compression of the mouse tibia. An advantage of loading the tibia is that changes are present in both the cancellous envelope of the proximal tibia and the cortical bone of the tibial diaphysis. To load the tibia of the mouse axially in vivo, a cyclic compressive load is applied up to five times a week to a single tibia per mouse for a duration lasting from 1 day to 6 weeks. With the contralateral limb as an internal control, the anabolic response of the skeleton to mechanical stimuli can be studied in a pairwise experimental design. Here, we describe the key parameters that must be considered before beginning an in vivo mouse tibial loading experiment, including methods for in vivo strain gauging of the tibial midshaft, and then we describe general methods for loading the mouse tibia for an experiment lasting multiple days.Item Potential influences on optimizing long-term musculoskeletal health in children and adolescents with X-linked hypophosphatemia (XLH)(Springer Nature, 2022-01-31) Glorieux, Francis H.; Bonewald, Lynda F.; Harvey, Nicholas C.; van der Meulen, Marjolein C. H.; Medicine, School of MedicineIn recent years, much progress has been made in understanding the mechanisms of bone growth and development over a lifespan, including the crosstalk between muscle and bone, to achieve optimal structure and function. While there have been significant advances in understanding how to help improve and maintain bone health in normal individuals, there is limited knowledge on whether these mechanisms apply or are compromised in pathological states. X-linked hypophosphatemia (XLH) (ORPHA:89936) is a rare, heritable, renal phosphate-wasting disorder. The resultant chronic hypophosphatemia leads to progressive deterioration in musculoskeletal function, including impaired growth, rickets, and limb deformities in children, as well as lifelong osteomalacia with reduced bone quality and impaired muscle structure and function. The clinical manifestations of the disease vary both in presentation and severity in affected individuals, and many of the consequences of childhood defects persist into adulthood, causing significant morbidity that impacts physical function and quality of life. Intervention to restore phosphate levels early in life during the critical stages of skeletal development in children with XLH could optimize growth and may prevent or reduce bone deformities in childhood. A healthier bone structure, together with improved muscle function, can lead to physical activity enhancing musculoskeletal health throughout life. In adults, continued management may help to maintain the positive effects acquired from childhood treatment, thereby slowing or halting disease progression. In this review, we summarize the opinions from members of a working group with expertise in pediatrics, epidemiology, and bone, joint and muscle biology, on potential outcomes for people with XLH, who have been optimally treated from an early age and continue treatment throughout life.