and diaphyseal BMC and vBMD. These changes, in combination with improvement in tibial cortical thickness and cross sectional area , resulted in an increase in tibial strength strain index . The radial SSI remained unchanged with treatment as there was no measurable improvement in radial geometry, but rather a maintenance of bone structure. Fostamatinib Figure 1 illustrates the improvement in trabecular volumetric bone mineral density at the 4 % site in both tibia and radius. This is the first report of bisphosphonate therapy in paediatric SCI and provides encouraging results on both trabecular and cortical bone. Zoledronic acid was able to reverse the loss of bone mass, density and bone strength in our patient.
The 18 month post treatment raw values increased in all the parameters measured even though in some of them the reversal was incomplete as the gain did not keep up with age matched reference data. As noted, bisphosphonate therapy in adult SCI has met with very limited success. Utilising the inherent anabolic effect of growth in children, bisphosphonate therapy Gamma-Secretase Inhibitors in the paediatric age group has the potential to influence the retention of primary trabecular and affect cortical modelling through the prevention of endocortical bone resorption. Although the positive effects of bisphosphonate therapy had been shown in children with osteogenesis imperfecta and secondary causes of osteoporosis, the benefit in children with flaccid paralysis had not been previously reported. During childhood, the amount of bone increases via three mechanisms: production of new trabeculae by endochondrial ossification, remodelling of trabecular bone with a positive balance and cortical bone modelling.
During endochondrial ossification, most pericardium of the primary trabeculae are removed during conversion to secondary trabeculae. Bisphosphonates inhibit bone resorption, thus more primary trabeculae survive to become secondary trabeculae. The overall trabecula number increases resulting in improvement of trabecular bone mineral density. Therefore, bisphosphonate treatment is able to preserve trabecular bone in children and may prevent fracture at the metaphyseal site which is rich in trabecular bone. After 18 months of treatment, this case demonstrated an increase in trabecular bone as evident by the increase in lumbar spine areal bone mineral density and BMC as well as trabecular vBMD and BMC in both tibia and radius.
Cortical thickness is determined by bone modelling where bone formation and bone resorption occur on opposite sides of the cortex. By inhibiting endocortical osteoclast bone resorption, zoledronic acid was able to positively affect cortical modelling in the tibia where there was an increase in cross sectional area and thickness. The reduction in cortical bone remodelling was evident by the increase in cortical vBMD in both tibia and radius. In adults, there is no cortical bone modelling as linear growth has ceased. Similarly endochondrial ossification does not occur, thus they do not make new trabecular bone at the metaphysis of the long bone or vertebrae. Bisphosphonate therapy therefore only reduces bone turnover on existing bone which may result in increased cortical vBMD but not cortical thickness. Bisphosphonate therapy in adult SCI has the potential to minimise on going immobilisation bone loss but will have little effect on established osteoporosis. There are still many unanswered questions in regards to determinants of bone health and clinical .