Early Alteration Of Serum MCP-1 Level Induced By Intermittent Administration Of PTH 1–34 In Postmenopausal Osteoporosis Women

ObjectiveOsteoporosis is a complex degenerative disease of bone metabolism,which is characterized by osteopenia,destruction of bone microstructure,increased fragility,decreased bone strength and increased risk of fracture.It can be divided into primary osteoporosis and secondary osteoporosis.Attesting to potency,daily subcutaneous injections of PTH 1-34 has been shown to produce significant improvement of bone strength by improving bone turnover and bone mineral density(BMD),thereby preventing and treating osteoporosis fracture.But its bone anabolic mechanism has not been fully revealed.We aimed to evaluate the osteogenic capacity of PTH 1-34 by measuring bone metabolism markers,and research the osteogenesis mechanism of PTH 1-34 by testing the early alterations of MCP-1,furtherly provide a new theoretical and experimental basis for the treatment of postmenopausal osteoporosis.MethodThe subjects recruited in this study were 20 postmenopausal osteoporosis patients collected from the orthopaedic outpatient department of native hospital from November 2018 to February 2019.All patients received a uniform treatment protocol: before PTH 1-34 injection,daily oral vitamin D 800 IU and calcium 1000 mg for at least three months was recorded as the control phase.Then daily subcutaneous injections of PTH 1-34 20 ?g with vitamin D and calcium taken orally as well,which was recorded as the treatment stage of PTH 1-34.Blood samples were collected at baseline,1 week,2week and 1month after initiation of treatment.Levels of specific serum bone-related markers: osteocalcin(OC),procollagen I N-terminal propeptide(PINP)and serum C-telopeptide of type 1 collagen(CTX)and chemokine CCL-2(MCP-1)was measured by ELISA.We use Dual energy x-ray absorptiometry(DXA)to measure lumber spine bone mineral density(BMD).All patients were provided sufficient informed consent,and the study was approved by the Committee on Human Research of native hospital.ResultThe average age of the enrolled subjects was 64.5±4.3 years old(mean ± SD),average weight was 64.3±6.4Kg,average height was 157±6.0cm,average BMI was 26.45±2.61Kg/?.After one month of PTH 1-34 treatment,the serum level of bone metabolism markers were significantly increased,which was statistically different from that in the control phase(P<0.05)and suggested that bone transformation,mainly bone formation,has been fully activated.However,there was no significant statistical difference in the bone mineral density(BMD)T value after 1 month of PTH 1-34 treatment compared with baseline.The serum MCP-1 concentration of subjects at control stage was 164±24 pg/mL,which increased to 236±48 pg/mL pg/mL 1 week after PTH 1-34 treatment.Then the concentration decreased to 172±34 pg/mL 2 weeks after PTH 1-34 treatment,which at 1 month was 165±26 pg/mL.This result suggested that the serum MCP-1 level reached the peak one week after intermittent PTH 1-34 injection,which had returned to the baseline level by two weeks and one month.ConclusionIntermittent administration of PTH 1-34 in the treatment of postmenopausal osteoporosis in the early stage can play a role in bone metabolism transformation and initiate the process of bone reconstruction.Serum MCP-1 level was transitorily elevated after intermittent PTH 1-34 treatment.Osteoclasts and precursor monocytes are recruited to the remodeling site induced by MCP-1 to initiate the process of bone remodeling.At the same time,MCP-1 facilitates the fusion of the pre-osteoclast forming mature osteoclasts through a paracrine mode.The stimulation of bone resorption during the anabolic protocol should be a transient event preceding osteoblastic bone formation to provide new remodeling sites for new incoming osteoblasts.In conclusion MCP-1 is a key molecular mediator for the anabolic effects of PTH 1-34 on bone.