title: Restoration of the coupling process and normalization of bone mass following successful treatment of endogenous Cushing's syndrome: a prospective, long-term study.
abstract: OBJECTIVE
  Endogenous Cushing's syndrome (CS) is associated with bone loss and an increased risk of fractures. However, the long-term outcome of treatment on bone health has not been adequately clarified.
  
  
  METHODS
  We followed 33 patients with active CS prospectively before and twice after treatment (mean follow-up 33 (n = 25) and 71 months (n = 18), respectively). The patients were compared to age-, sex- and body mass index (BMI)-matched controls, also followed longitudinally.
  
  
  METHODS
  Bone mineral indices (bone mineral density (BMD), bone mineral content (BMC) and bone area) were evaluated in the lumbar spine (LS), femoral neck (FN), and total body (TB) by dual-energy X-ray absorptiometry (DXA). Biochemical markers of bone turnover were assessed by serum levels of osteocalcin and C-terminal telopeptides of Type-1 collagen (CTX-1).
  
  
  RESULTS
  Mann-Whitney rank sum tests showed that BMD of the LS, FN and TB was reduced by 14.8% (P < 0.001), 15.7% (P < 0.001), and 9.2% (P < 0.001) in CS vs. controls at baseline, with markedly reduced serum osteocalcin (P = 0.014) and increased CTX-1 (P = 0.012) levels, but no correlation between markers. At first follow-up, BMD was increased in LS (7.9%, P < 0.001) and FN (3.5%, P = 0.003) compared to baseline. The time-dependent rise in BMD (LS (r = 0.59; P = 0.002) and FN (r = 0.52; P = 0.007); Spearman's rank correlation), in CS was paralleled by increased osteocalcin (275%, P < 0.001) and correlation between biochemical markers (r = 0.92, P < 0.001; Pearson's correlation). TB BMD did not increase significantly before the second follow-up, when BMD Z-scores were normalized in all three compartments.
  
  
  CONCLUSIONS
  Our observations demonstrate restoration of coupled bone remodeling and normalization of bone mineral density in all measured skeletal compartments of treated CS patients after prolonged recovery, first significant in predominantly trabecular bone (i.e. lumbar spine).
authors.affiliation: Section of Endocrinology, Rikshospitalet University Hospital, Oslo, Norway. cybele.kristo@rikshospitalet.no
authors.forename: Cybèle
authors.initials: C
authors.lastname: Kristo
authors.forename: Rune
authors.initials: R
authors.lastname: Jemtland
authors.forename: Thor
authors.initials: T
authors.lastname: Ueland
authors.forename: Kristin
authors.initials: K
authors.lastname: Godang
authors.forename: Jens
authors.initials: J
authors.lastname: Bollerslev
mesh_terms: D000315:Adrenalectomy; D000328:Adult; D015519:Bone Density / Q000502:physiology*; D016723:Bone Remodeling / Q000502:physiology*; D001842:Bone and Bones / Q000378:metabolism; D003480:Cushing Syndrome / Q000503:physiopathology / Q000601:surgery*; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies