Effect of bisphosphonate therapy and parathyroidectomy on the urinary excretion of galactosylhydroxylysine in primary hyperparathyroidism.
BACKGROUND
In patients with mild or asymptomatic primary hyperparathyroidism a reliable index of bone resorption might be useful for appropriate management. Hydroxyproline is the most commonly used marker of bone resorption but its low specificity and sensitivity are known. Galactosylhydroxylysine, an amino acid mainly represented in bone collagen, has been proposed as a more suitable index of bone resorption. In this study we evaluated the sensitivity of galactosylhydroxylysine and hydroxyproline assays in following the changes of their urinary levels in 12 patients with mild primary hyperparathyroidism before and after treatment with bisphosphonate and surgery.


METHODS
Serum and fasting urine specimens were obtained from 12 women with mild primary hyperparathyroidism before and after bisphosphonate treatment (2.5 mg daily for 5 days, intravenously) and after a further 25 days; in 7 patients biochemical tests were also performed 1 and 6 days after parathyroidectomy. Galactosylhydroxylysine was assayed by an HPLC method and hydroxyproline by a RIA commercial kit.


RESULTS
Baseline galactosylhydroxylysine urinary levels were far above the normal range in all the patients whilst in 8 of them baseline hydroxyproline levels were normal. Bisphosphonate treatment significantly decreased bone turnover as shown by a significant fall in serum calcium (from 2.9 to 2.6 mmol/l; P < 0.001) and in galactosylhydroxylysine and hydroxyproline (-55 and -31% respectively). Twenty-five days after the end of treatment, resorption increased again and serum calcium and galactosylhydroxylysine, but not hydroxyproline, rose significantly towards basal levels. One day after parathyroidectomy serum calcium, galactosylhydroxylysine and PTH showed reduction below normal ranges. PTH and galactosylhydroxylysine returned to normal values at day 6 after parathyroidectomy. No changes in hydroxyproline levels were seen. Galactosylhydroxylysine, but not hydroxyproline, correlated significantly with serum calcium and PTH.


CONCLUSIONS
Galactosylhydroxylysine appears to be a sensitive index of bone resorption, useful in the clinical assessment of bone involvement and in the management of patients with mild primary hyperparathyroidism.
LoCascio
V
V
Instituti di Semeiotica e Nefrologia Medica, Università di Verona, Italy.
Braga
V
V
Bertoldo
F
F
Bettica
P
P
Pasini
A F
AF
Stefani
L
L
Moro
L
L
D000368:Aged; D019386:Alendronate; D015415:Biomarkers / Q000652:urine; D001862:Bone Resorption / Q000652:urine; D004164:Diphosphonates / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006901:Hydroxylysine / Q000031:analogs & derivatives* / Q000652:urine; D006909:Hydroxyproline / Q000652:urine; D006961:Hyperparathyroidism / Q000188:drug therapy* / Q000652:urine; D008875:Middle Aged; D016105:Parathyroidectomy
D015415:Biomarkers; D004164:Diphosphonates; D006901:Hydroxylysine; C007817:galactosylhydroxylysine; D006909:Hydroxyproline; D019386:Alendronate