| Purpose: Explore the therapeutic effect of intermittent teriparatide administration on Kummell’s disease and examine the changes of circulating mesenchymal stem cells(MSCs)in patients with Kummell’s disease during the course of drug administration.Methods: 1.To evaluate the therapeutic effect of intermittent teriparatide administration on Kummell disease: firstly,49 patients who met the diagnostic criteria of Kummell disease and had refused surgery operation were selected and randomly divided into teriparatide group(n= 24)and osteoporosis group(n= 25).Neurological function was evaluated using modified Japanese Orthopedic Association(mJOA)score(11-point scale,the maximum score of 11 implies normalcy).Visual analog scale(VAS)scores,kyphotic angles,anterior-border heights and diameters of the spinal canal of the fractured vertebrae,spine bone mineral density(BMD),and plasma markers of bone resorption and bone formation were also examined at baseline,6 and 12 months after initiation of the medication regimen.2.To evaluate the effect of intermittent teriparatide administration on circulating mesenchymal stem cells: the peripheral blood of patients with Kummell’s disease was collected at baseline and 1,3,6,and 12 months after intermittent teriparatide administration,and the number of MSCs in circulation was measured by flow cytometry;Randomly selected 6 patients from the teriparatide group and extracted 5 ml peripheral blood at baseline and 1 month after intermittent teriparatide administration.MSCs were isolated from the patient’s peripheral blood and identified by flow cytometry.The isolated circulating MSCs were cultured in osteogenic medium to teste their osteogenic differentiation ability.Results: 2.At 12 months,Mean concentrations of bone formation and bone resorption biomarkers,mean spine BMD,and mean anterior-border height and spinal canal diameter of the fractured vertebrae were significantly greater in the teriparatide group than in the alendronate group.Mean VAS score,mean kyphotic angle of the fractured vertebrae were significantly smaller in the teriparatide group than in the alendronate group.At 12 months,the mean values of all parameters related to vertebral stability(mean values of posterior convex Angle of fractured vertebrae,mean values of anterior margin height of fractured vertebrae,and vertebral canal diameter)in patients in the tripitappeptide group were significantly better than the mean values of corresponding parameters in the bisphosphonate group.While the mean values of all parameters related to bone mass and bone strength(mean BMD and mean PINP concentration in plasma)in the tripareptide group were significantly better than those in the bisphosphonate group.2.The number of MSCs in the circulation of Kummell disease patients was significantly higher than that of the patients at baseline after intermittent injection of tripareptide.However,there was no significant difference in the number of MSCs in the circulation of patients in the bisphosphate group after administration compared with the number of MSCs in the circulation of patients at baseline.The expression levels of collagen 1,osteocalcin,runx-2 and OSX in MSCs were continuously up-regulated during the induction of osteogenic differentiation of MSCs.The expression levels of osteogenic genes in circulating MSCs obtained at 1 month after intermittent triptapeptide administration were significantly higher than those at baseline.The alkaline phosphatase staining positive area and the alkaline phosphatase activity of osteogenesis induced circulating MSCs obtained at 1 month after intermittent triptapeptide administration were significantly higher than those of osteogenesis induced circulating MSCs obtained at baseline.The size of mineral nodules and the volume of calcium salt deposition in the osteogenesis induced circulating MSCs obtained at 1 month after intermittent triptapeptide administration were significantly higher than those in osteogenesis induced circulating MSCs obtained at baseline.Conclusions: 1.Intermittent administration of tripitapeptide has a significantly better therapeutic effect on Kummell disease than oral bisphosphate;Conservative treatment with triptapeptide can significantly relieve pain,enhance bone strength and prevent the progression of spinal cord compression.2.The results of this study showed that intermittent administration of triptapeptide increased the number of MSCs in the circulation of Kummell disease patients and the osteogenic differentiation ability of the circulating MSCs in vitro 1 month after intermittent teriparatide administration. |
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