The co-operation between p50 and p52 is best depicted in the genetic knockout mice, where p50 and p52 single deletions showed no developmental defects, whereas double deletion of these genes resulted in severe impairment in bone development [ 20, 21].
In both humans and mice, loss of IGF-1 action is manifested with severe intrauterine growth retardation and delayed bone development.
Morquio syndrome, also called mucopolysaccharidosis IV, rare hereditary disorder of intracartilaginous bone development that results in severe malformation of the skeleton (particularly the spine and long bones) and dwarfing.
Both patients where wheelchair-bound at adult age, with very short stature, severe bone involvement and normal intellectual and neurological development [ 10].
Recently, it was demonstrated that depletion of the receptors for thyroid hormones, mimicking hypothyroidism, results in severe distortions of the growth plate and delayed bone development [3,4].
Depending on the nature of the particles, the immune reaction can entail harsh reactions such as the development of acute and chronic inflammation, severe bone loss around the implants, and ultimately implant loosening.
Delayed bone development in juvenile Thra1 PV /+ mice (21) led to severe skeletal abnormalities in adults.
One of the major clinical features of myeloma is the development of a progressive and destructive osteolytic bone disease, associated with severe bone pain, pathological fractures, osteoporosis, hypercalcemia and spinal cord compression.
Additionally, severe bone alterations were observed with time, and the double mutant developed severe kyphosis.
MIP-1α was also found to be elevated in the serum of myeloma patients with severe bone disease and correlated positively with bone resorption markers, providing evidence for a causal role of the chemokine in the development of lytic bone lesions in myeloma [ 26, 27].
