Impact of Intrinsic Muscle Weakness on Muscle–Bone Crosstalk in Osteogenesis Imperfecta

Abstract

Bone and muscle are highly synergistic tissues that communicate extensively via mechanotransduction and biochemical signaling. Osteogenesis imperfecta (OI) is a heritable connective tissue disorder of severe bone fragility and recently recognized skeletal muscle weakness. The presence of impaired bone and muscle in OI leads to a continuous cycle of altered muscle–bone crosstalk with weak muscles further compromising bone and vice versa. Currently, there is no cure for OI and understanding the pathogenesis of the skeletal muscle weakness in relation to the bone pathogenesis of OI in light of the critical role of muscle–bone crosstalk is essential to developing and identifying novel therapeutic targets and strategies for OI. This review will highlight how impaired skeletal muscle function contributes to the pathophysiology of OI and how this phenomenon further perpetuates bone fragility.

Functional Independence of Taiwanese Children with Osteogenesis Imperfecta

“…Previous studies have reported that upper-extremity deformities affect the performance of basic self-care tasks and impact mobility, transfers, and ambulation, especially in children with severe OI [ 27 ]. Moreover, patients with OI have a low muscle size [ 12 , 28 ], lower limb muscle weakness [ 12 , 29 , 30 , 31 , 32 , 33 , 34 ], restricted joint range of motion [ 32 , 35 ], pain [ 36 , 37 ] and fear of fractures when bearing weight [ 36 , 38 ]; all of which could cause obstacles in accomplishing these daily tasks and have a great impact on the functional independence of these patients.…”

Bone Mass, Density, Geometry, and Stress–Strain Index in Adults With Osteogenesis Imperfecta Type I and Their Associations With Physical Activity and Muscle Function Parameters

“…(6)(7)(8)(9) Although physical activity is shown to be one of the major determinants of bone mass and resistance to fractures in a healthy population, studies evaluating bone parameters in OI did not take physical activity into account. (10,11) Therefore, the association of physical activity with bone parameters in OI remains currently unclear.…”

“…(16,17) In children with OI, conflicting results, ranging from reduced to normal biomechanical responsiveness, have been reported. (4,10,14) Exploring this relationship between muscle and bone is of clinical importance, as it permits to assess whether muscle-centered therapeutic strategies (eg, exercise, muscle strengthening, and whole-body vibration therapy) could improve bone strength in OI. (10,14,18) However, to our knowledge, no studies have evaluated the association between muscle and bone parameters in adults with OI type I.…”

“…In addition to bone deficits, muscle weakness is a frequently reported feature in children and adolescents with OI. (10,(12)(13)(14)(15) Possible underlying mechanisms include altered collagen structure and function, reduced mobility, and decreased physical activity (due to periods of immobilization, pain, and fear of movement), but the role of altered biomechanical interactions between muscle and bone is of increasing interest. (10) An elevated mechanostat setpoint in OI has been postulated because of the collagen defect.…”

“…(10,(12)(13)(14)(15) Possible underlying mechanisms include altered collagen structure and function, reduced mobility, and decreased physical activity (due to periods of immobilization, pain, and fear of movement), but the role of altered biomechanical interactions between muscle and bone is of increasing interest. (10) An elevated mechanostat setpoint in OI has been postulated because of the collagen defect. (16,17) In children with OI, conflicting results, ranging from reduced to normal biomechanical responsiveness, have been reported.…”