A Retrospective Analysis Of The Efficacy And Safety Of Bisphosphonates In Treatment Of Fibrous Dysplasia

ObjectiveTo investigate the clinical characteristics of patients with fibrous dysplasia in the Department of Endocrinology of Peking Union Medical College Hospital and to evaluate the efficacy and safety of bisphosphonates.Subjects and methodsThe clinical data of FD patients treated in our department from January 2000 to June 2016 were analyzed retrospectively.The efficacy and safety of bisphosphonates in patients receiving bisphosphonates(BPs)treatment and with more than half a year follow-up data were evaluated.The clinical data including baseline symptoms,signs,biochemical parameters,bone turnover markers and imaging fingding were collected.For the treatment group,bisphosphonates use and the change of clinical symptoms(pain,fracture)and bone turnover markers were recorded,along with the adverse events after BPs therapy.Results1.A total of 47 FD patients were enrolled,with an average onset age of 6 years(2-10 years),male:female =19:28,and the average course of disease was 5(2,16)years.Among them,42 cases(89.4%)were polyostotic fibrous dysplasia(PFD),and McCune-Albright syndrome(MAS)was diagnosed in 40 cases.There were 21 cases with bone pain,40 cases with bone deformity,and 19 cases with pathological fractures.39 cases had Cafe-au-lait pigmentation.33 cases had endocrine hyperfunction,among which peripheral precocious puberty was the most common(42.6%).The average levels of serum alkaline phosphatase(ALP)in the 47 patients were 406.75 ± 423.26U/L in adults and 655.96 ± 445.65U/L in children.2.Efficacy and safety of bisphosphonates:n= 231)Monostotic fibrous dysplasia:1 case,pain free,with once intravenous pamidronate treatment.The levels of ALP before and after BPs treatment were normal.2)Polyostotic fibrous dysplasia:22 cases,all associated with MAS.Most of the cases(21)received intravenous BPs treatment,including 10 cases with pamidronate and 11 cases with zoledronic acid,respectively.Only one case received oral alendronate.(1)Baseline characteristics:average onset age was 5.4±5.5 years,female:male=8:3,the course of disease was 7.7±7.6 years.At baseline,bone pain,fractures,and skeletal malformation was observed in 50%,50%,and 82%of the patients,respectively.The baseline ALP level was 706.41±444.83U/L.(2)Efficacy of BPs treatment:?Clinical symptom:After the first medication,partial or complete remission of bone pain was found in 64%(7/11)of patients.?Bone turnover markers:ALP level change:After the first medication,ALP level decreased by 30.32%after oral alendronate in one patient.ALP change rates in the pamidronate and zoledronic acid group were-22.67±16.90%and-34.13±26.33%,respectively,with no significant difference(P=0.256).There were ten patients receiving more than once BPs treatments:Compared to baseline,ALP change rates after the last treatment and first treatment were-27.90±24.14%and-24.06±18.03%,respectively,with no significant difference(P=0.663).?-CTX level change:There were 8 patients receiving zoledronic acid,and the change rate of serum C-terminal telopeptide of type I collagen was-37.57±20.35%.?Factors affecting the therapeutic effect of BPs:ALP change rate was not found to be related to onset age,course of disease,presence of peripheral sexual precocity,pituitary growth hormone-secreting tumor,the number of affected bones and presence of hyperphosphatemia after the first medication.(3)Safety:the main adverse effects of bisphosphonates included transient fever,myosalgia,and hypocalcemia.After one year of initial BPs treatment,no impairment of liver and kidney was found.The side effect on height was not found after the first BPs therapy in childhood patients.ConclusionsHigh bone turnover was observed in symptomatic FD patients,characterized by significantly elevated levels of serum ALP and ?-CTX.After bisphosphonates treatment,bone pain improved,with serum ALP and ?-CTX levels decreased significantly,suggesting that bisphosphonates might control the activity of the disease by inhibiting high bone turnover.The adverse effects of BPs were mild,and well tolerated in most of the patients.