title: The cumulative incidence of and risk factors for latent beaking in patients with autoimmune diseases taking long-term glucocorticoids and bisphosphonates.
abstract: CONCLUSIONS
  The incidence of beaking, which has been reported to precede atypical femoral fracture, was high and increased over 2 years in patients with autoimmune diseases who were taking bisphosphonates and glucocorticoids. Regular femoral X-rays are strongly recommended to screen for beaking, and bisphosphonate drug holidays should be considered.
  
  
  BACKGROUND
  Atypical femoral fractures (AFFs) have been recently recognized as complications associated with bisphosphonate (BP) use. AFFs are considered to be stress fractures; localized periosteal thickening of the lateral cortex is often present at the fracture site; this thickening is termed "beaking." Beaking has been reported to precede AFF. The aims of the present study were to evaluate the incidence of latent beaking in patients with autoimmune diseases taking BPs and glucocorticoids and to identify risk factors for beaking.
  
  
  METHODS
  A total of 125 patients with autoimmune diseases who were taking BPs and glucocorticoids was included; 116 patients underwent X-rays and analysis of serum and urine bone metabolic markers annually for 2 years. Mean patient age was 54.5 years; there were 105 (90.5%) females and the mean duration of disease was 13.2 years. Focal lateral cortical thickening in femoral X-rays was defined as beaking.
  
  
  RESULTS
  Beaking was detected in 15 femora of 10 patients (8.0%) at the time of recruitment. Over the 2-year observation period, the incidence of beaking increased to 21 femora of 12 patients (10.3%), and a complete AFF at the location of beaking occurred in one patient. Beaking was associated with a longer duration of BP treatment (6.1 ± 1.0 years vs. 5.0 ± 2.9 years, p = 0.01). Age 40-60 years, BP therapy ≥4 years, and diabetes mellitus were significantly associated with beaking.
  
  
  CONCLUSIONS
  The incidence of beaking was high, and increased over 2 years, in patients with autoimmune diseases who were taking BPs and glucocorticoids. Regular femoral X-rays are strongly recommended to screen for beaking. Long-term BP/glucocorticoid use was a risk factor for beaking in patients with autoimmune diseases; BP drug holidays should be considered.
authors.affiliation: Division of Clinical Nephrology and Rheumatology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachi-Dori, Chuoku, Niigata City, 951-8510, Japan. hiroe-212@umin.ac.jp.
authors.forename: H
authors.initials: H
authors.lastname: Sato
authors.affiliation: Division of Orthopedic Surgery, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachi-Dori, Chuoku, Niigata City, 951-8510, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Kondo
authors.affiliation: Division of Clinical Nephrology and Rheumatology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachi-Dori, Chuoku, Niigata City, 951-8510, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Wada
authors.affiliation: Division of Clinical Nephrology and Rheumatology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachi-Dori, Chuoku, Niigata City, 951-8510, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Nakatsue
authors.affiliation: Division of Clinical Nephrology and Rheumatology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachi-Dori, Chuoku, Niigata City, 951-8510, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Iguchi
authors.affiliation: Division of Orthopedic Surgery, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachi-Dori, Chuoku, Niigata City, 951-8510, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Fujisawa
authors.affiliation: Division of Clinical Nephrology and Rheumatology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachi-Dori, Chuoku, Niigata City, 951-8510, Japan.
authors.forename: J J
authors.initials: JJ
authors.lastname: Kazama
authors.affiliation: Health Administration Center, Niigata University, 2-8050 Ikarashi, Nishiku, Niigata City, 950-2181, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kuroda
authors.affiliation: Department of Medical Technology, School of Health Sciences, Faculty of Medicine, Niigata University, 2-746 Asahimachi-Dori, Chuoku, Niigata City, 951-8518, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Nakano
authors.affiliation: Division of Orthopedic Surgery, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachi-Dori, Chuoku, Niigata City, 951-8510, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Endo
authors.affiliation: Division of Clinical Nephrology and Rheumatology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachi-Dori, Chuoku, Niigata City, 951-8510, Japan.
authors.forename: I
authors.initials: I
authors.lastname: Narita
mesh_terms: D015502:Absorptiometry, Photon / Q000379:methods; D000328:Adult; D000368:Aged; D001327:Autoimmune Diseases / Q000188:drug therapy*; D015415:Biomarkers / Q000378:metabolism; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D048909:Diabetes Complications / Q000000981:diagnostic imaging / Q000378:metabolism; D004164:Diphosphonates / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D004334:Drug Administration Schedule; D005260:Female; D005264:Femoral Fractures / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000378:metabolism; D015775:Fractures, Stress / Q000139:chemically induced* / Q000000981:diagnostic imaging / Q000378:metabolism; D005938:Glucocorticoids / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D011859:Radiography; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D005938:Glucocorticoids
keywords: Atypical femoral fracture; Beaking; Bisphosphonate; Glucocorticoid