title: Effects of calcitriol on parathyroid function and on bone remodelling in secondary hyperparathyroidism.
abstract: BACKGROUND
  Secondary hyperparathyroidism (2HPT) develops in chronic renal failure due to disturbances of calcium, phosphorus and vitamin D metabolism. It is characterized by high turnover bone disease and an altered calcium-parathyroid hormone (PTH) relationship. Calcitriol has been widely used for the treatment of 2HPT. However, it remains controversial whether calcitriol is capable of inducing changes of the calcium-PTH curve. The aim of the present study was to examine this issue and to determine the effect of calcitriol on bone remodelling in patients with severe 2HPT.
  
  
  METHODS
  We evaluated 16 chronic haemodialysis patients with severe 2HPT (PTH 899+/-342 pg/ml). Each patient underwent a dynamic parathyroid function test (by infusion of calcium gluconate and sodium citrate) and a bone biopsy before and after a 6 month period of i.v. calcitriol therapy (CTx).
  
  
  RESULTS
  After treatment, eight patients were identified as calcitriol responders and the other eight as non-responders, based on plasma PTH level (<300 pg/ml for responders and >300 pg/ml for non-responders). The first group had higher plasma 25OHD(3) levels (39+/-8 vs 24+/-7 ng/ml, P<0.005). As to the calcium-PTH curve, we found differences in slope (-12.7+/-5.2 vs -21.7+/-11.4, P=0.05), basal/maximum PTH ratio (48.8+/-14.9 vs 71.05+/-20.1%, P=0.01) and time to achieve hypocalcaemia (79.0+/-13.5 vs 94.3+/-13.7 min, P<0.001). Initial histomorphometric parameters did not allow identification of the different groups. After the 6-month CTx, alterations in the calcium-PTH curve were clearly seen in responders [a drop in maximum PTH (from 1651+/-616 to 938+/-744 pg/ml, P<0.05) and minimum PTH (from 163+/-75.4 to 102.2+/-56.7 pg/ml, P<0.005)], associated with an increase in minimum/basal PTH ratio (from 23.3+/-11.6 to 34.5+/-20.4%, P<0.05) and maximum calcium (from 0.99+/-0.07 to 1.1+/-0.09 mmol/l, P<0.05). Set point and slope were not altered after calcitriol treatment, in responders (set point=1.17+/-0.08 vs 1.15+/-0.1 mmol/l, ns; slope=-12.7+/-5.2 vs -12.9+/-9.3, ns) or non-responders (set point=1.21+/-0.05 vs 1.21+/-0.2 mmol/l, ns; slope=-21.7+/-11.4 vs -17.3+/-8.4, ns). Bone formation parameters were reduced in all patients [osteoid surface (OS/BS)=from 57.1+/-21.6 to 41.6+/-26%, P<0.05 for responders, and from 76.7+/-12 to 47.1+/-15%, P<0.001 in non-responders], but non-responders had increased bone resorption [eroded surface (ES/BS)=7.1+/-3.4 vs 16.6+/-4.9, P<0.05].
  
  
  CONCLUSIONS
  Calcitriol had non-uniform effects on parathyroid function and bone remodelling in uraemic patients. Non-responders exhibited a decoupled remodelling process that could further influence mineral balance or possibly also bone structure. To avoid such undesirable effects, early identification of non-responder patients is crucial when using calcitriol for the treatment of 2HPT.
authors.affiliation: Nephrology Department, School of Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: André Falcão Pedrosa
authors.initials: AF
authors.lastname: Costa
authors.forename: Luciene Machado
authors.initials: LM
authors.lastname: dos Reis
authors.forename: Melani Custódio
authors.initials: MC
authors.lastname: Ribeiro
authors.forename: Rosa Maria Affonso
authors.initials: RM
authors.lastname: Moysés
authors.forename: Vanda
authors.initials: V
authors.lastname: Jorgetti
mesh_terms: D000328:Adult; D016723:Bone Remodeling / Q000187:drug effects*; D002117:Calcitriol / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D007262:Infusions, Intravenous; D007676:Kidney Failure, Chronic / Q000175:diagnosis / Q000628:therapy; D008297:Male; D008875:Middle Aged; D010280:Parathyroid Glands / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011336:Probability; D011379:Prognosis; D011446:Prospective Studies; D006435:Renal Dialysis / Q000009:adverse effects* / Q000379:methods; D018570:Risk Assessment; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D002117:Calcitriol