title: Factors associated with bisphosphonate treatment failure in postmenopausal women with primary osteoporosis.
abstract: Among 97 postmenopausal women with primary osteoporosis, adequate calcium and vitamin D supplementation, and good compliance to a 36-month bisphosphonate treatment, the 25.8% of patients are inadequate responders. Current smoking and a bone turnover in the upper part of the normal range increase the risk of treatment failure.
  
  
  BACKGROUND
  To evaluate the prevalence of the bisphosphonate treatment failure and its possible associated factors in women with primary osteoporosis (PO).
  
  
  METHODS
  We studied 97 previously untreated postmenopausal women with PO and fragility fractures and/or a FRAX® 10-year probability of a major osteoporotic fracture ≥ 7.5%, before and after a 36-month treatment with alendronate or risedronate and adequate vitamin D supplementation with good compliance. At baseline and after 36 months, lumbar spine (LS) and femoral bone mineral density (BMD) were assessed by Dual X-ray absorptiometry and vertebral fractures by spinal radiographs. Spinal deformity index (SDI) was calculated. Treatment failure was defined by the presence of ≥ 2 incident fragility fractures and/or a BMD decrease greater than the least significant change.
  
  
  RESULTS
  Bisphosphonate treatment failure was observed in 25.8% of patients. Age, body mass index, years since menopause, familiar history of hip fracture, number of falls, type of bisphosphonate used, 25-hydroxyvitamin D levels (25OHVitD), BMD, SDI, and FRAX® score at baseline were not different between responders and inadequate responders. Treatment failure was associated with current smoking (OR 3.22, 95% CI 1.10-9.50, P = 0.034) and baseline alkaline phosphatase total activity levels ≥ 66.5 U/L (OR 4.22, 95% CI 1.48-12.01, P = 0.007), regardless of age, number of falls, LS BMD, and baseline SDI.
  
  
  CONCLUSIONS
  The 25.8 % of PO postmenopausal women inadequately responds to bisphosphonates, despite a good compliance to therapy and normal 25OHVitD levels. The current smoking and bone turnover in the upper part of the normal range are associated with the inadequate response to bisphosphonates.
authors: Unit of Endocrinology and Metabolic Diseases, Department of Clinical Sciences and Community Health, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, University of Milan, Padiglione Granelli, Via F. Sforza 35, 20122, Milan, Italy, elisa.cairoli@live.it.
authors: E
authors: E
authors: Cairoli
authors: C
authors: C
authors: Eller-Vainicher
authors: F M
authors: FM
authors: Ulivieri
authors: V V
authors: VV
authors: Zhukouskaya
authors: S
authors: S
authors: Palmieri
authors: V
authors: V
authors: Morelli
authors: P
authors: P
authors: Beck-Peccoz
authors: I
authors: I
authors: Chiodini
mesh_terms: D015502:Absorptiometry, Photon / Q000379:methods; D000368:Aged; D000369:Aged, 80 and over; D019386:Alendronate / Q000627:therapeutic use; D000469:Alkaline Phosphatase / Q000097:blood; D015415:Biomarkers / Q000097:blood; D015519:Bone Density / Q000187:drug effects / Q000502:physiology; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D016723:Bone Remodeling / Q000187:drug effects / Q000502:physiology; D004164:Diphosphonates / Q000627:therapeutic use*; D012968:Etidronic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D005260:Female; D005272:Femur Neck / Q000503:physiopathology; D005500:Follow-Up Studies; D006621:Hip Joint / Q000503:physiopathology; D006801:Humans; D008159:Lumbar Vertebrae / Q000503:physiopathology; D055118:Medication Adherence; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy* / Q000503:physiopathology; D058866:Osteoporotic Fractures / Q000503:physiopathology / Q000517:prevention & control*; D000068296:Risedronic Acid; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D017211:Treatment Failure
chemical_list: D015415:Biomarkers; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D000469:Alkaline Phosphatase; D000068296:Risedronic Acid; D012968:Etidronic Acid; D019386:Alendronate