hydroxylysine and Hyperparathyroidism

The aims of this study were to determine 1) whether primary hyperparathyroidism (PHPT) is associated with accelerated bone loss in postmenopausal women, 2) whether bone mineral density (BMD) and bone turnover change to a similar extent with surgery and hormone replacement therapy (HRT) in these patients, and 3) whether biochemical markers of bone turnover measured at baseline can be used to predict the change in BMD in these patients after different therapies. We studied 33 postmenopausal women with PHPT; their ages at the time of study ranged from 48-80 yr (mean +/- SD, 63 +/- 10). Total body (TB), lumbar spine (LS), and femoral neck (FN) BMD and biochemical markers of bone turnover were measured at baseline and 10-30 months (19 +/- 5) after parathyroid surgery, HRT, or no treatment. BMD was measured in 33 age-matched healthy controls at baseline and at a mean of 24 months. Baseline biochemical markers of bone turnover were measured in controls. In PHPT at baseline, the mean z-score of BMD was -1.25 at TB (95% confidence interval, -1.64 to -0.86), -0.95 at LS (-1.37 to -0.53), and -1.30 at FN (-1.65 to -0.95), whereas the mean z score was 0.45 for serum carboxy-terminal propeptide of human type I procollagen (0.02-0.89), 1.05 for bone alkaline phosphatase (0.38-1.71), 2.38 for 24-h urinary excretion of cross-linked N-terminal telopeptide of type I collagen (NTx; 1.63-3.13), and 2.36 for 24-h urinary excretion of galactosyl hydroxylysine (1.97-2.74). After surgery and HRT, BMD increased and bone turnover decreased during the follow-up. In the untreated group, BMD decreased at TB and FN, and levels of bone alkaline phosphatase, NTx/creatinine, and galactosyl hydroxylysine/creatinine increased. When the rate of change in BMD (percentage per yr) was compared with that in the control group, bone gain was significant at all three skeletal sites after surgery and HRT, and bone loss was significant at TB and FN, but not at LS, in the untreated group. There was a weak, but significant, correlation between baseline urinary NTx and the change in femoral neck BMD in the untreated group (r = -0.36; P = 0.05). We conclude that untreated postmenopausal women with PHPT have low BMD resulting from accelerated bone loss at the TB and FN. Surgery and HRT both restore BMD and bone turnover toward normal in postmenopausal women with PHPT. A single measurement of bone turnover is insufficient to predict BMD changes in individual patients with PHPT.

Topics: Aged; Aged, 80 and over; Alkaline Phosphatase; Bone Density; Bone Remodeling; Collagen; Collagen Type I; Creatinine; Estrogen Replacement Therapy; Female; Humans; Hydroxylysine; Hyperparathyroidism; Middle Aged; Peptide Fragments; Peptides; Postmenopause; Procollagen

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.. 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.. 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.. 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.

Topics: Aged; Alendronate; Biomarkers; Bone Resorption; Diphosphonates; Female; Humans; Hydroxylysine; Hydroxyproline; Hyperparathyroidism; Middle Aged; Parathyroidectomy

The pyridinium derivatives hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP) are intermolecular crosslinking compounds of collagen which are only present in its mature form. Contrasting to the wide distribution of type I and II collagens, HP and LP are absent from skin, ligament and fascia, and their major sources are bone and cartilage. Using a specific HPLC assay, we have determined the 24-h excretion of HP and LP crosslinks in normal adults of both sexes, in patients with primary hyperparathyroidism and in patients with Paget's disease of bone before and after intravenous treatment with amino-propylidene bisphosphonate (APB). Mean adult normal values were 33 +/- 13 pmol/mumol creatinine for HP and 6.3 +/- 3.4 pmol/mumol creatinine for LP. In women, menopause induced a 2-3-fold increase of HP and LP reflecting the well documented postmenopausal increase of bone turnover. In the urine of patients with primary hyperparathyroidism and of patients with active Paget's disease of bone, urinary crosslinks were significantly higher than in age-matched controls, with a mean 3- and 12-fold increase, respectively. Urinary excretion of hydroxyproline is a well recognized but poorly sensitive marker of bone turnover, reflecting resorption. In the same patients, the effect of menopause and disease state on hydroxyproline excretion was much less dramatic than on HP and LP. During intravenous APB treatment of pagetic patients, there was an early decrease of HP and LP, which was significant after 24 h and reached 62% at 4 days, contrasting with a late and milder decrease of urinary hydroxyproline. Because APB is a potent inhibitor of resorption which does not have a direct short-term effect on bone formation, these data also indicate that urinary excretion of HP and LP reflect only collagen degradation occurring during osteoclastic resorption and not the degradation of newly synthesized collagen. We conclude that urinary HP and LP excretion represents the first sensitive and specific marker of bone resorption. Its use should be valuable in the clinical investigation of metabolic bone diseases, especially osteoporosis.

Topics: Adult; Aged; Alkaline Phosphatase; Amino Acids; Bone Diseases, Metabolic; Bone Resorption; Chromatography, High Pressure Liquid; Female; Humans; Hydroxylysine; Hyperparathyroidism; Lysine; Male; Menopause; Middle Aged; Osteitis Deformans; Pyridinium Compounds; Reference Standards

The urinary excretion of glucosyl-galactosyl-hydroxylysine and of galactosyl-hydroxylysine were studied in Paget's disease of bone and in primary hyperparathyroidism. Both metabolites were increased in these diseases. Although glucosyl-galactosyl-hydroxylysine is not abundant in bone collagen, it is possible that a part of it originates from calcified tissue.

Topics: Alkaline Phosphatase; Bone and Bones; Calcitonin; Collagen; Glycosides; Humans; Hydroxylysine; Hyperparathyroidism; Osteitis Deformans

Topics: Adult; Bone Diseases; Calcitonin; Chromatography, Ion Exchange; Creatinine; Disaccharides; Female; Galactose; Glycosides; Glycosuria; Humans; Hydroxylysine; Hyperparathyroidism; Male; Monosaccharides; Osteitis Deformans; Osteomalacia; Parathyroid Glands; Protein Binding; Skin Diseases