Gender variation in PTH sensitivity and rhythmicity following growth hormone replacement in adult growth hormone‐deficient patients

Abstract

BACKGROUND Adult GH deficiency (AGHD) is associated with osteoporosis and reduced bone turnover;factors improved by GH replacement (GHR), with men gaining greater benefit than women. Reduction in sensitivity of bone and kidney to the effects of PTH may underlie AGHD changes in bone turnover. We determined the gender difference in PTH target-organ sensitivity following GHR in AGHD patients. DESIGN , PATIENTS AND MEASUREMENTS Twenty AGHD patients (10 men) were admitted to hospital before and after GHR initiation. Half-hourly blood samples were collected for PTH, calcium, nephrogenous cyclic AMP (NcAMP, marker of PTH activity), type-I collagen C-telopeptide (CTX, bone resorption marker) and procollagen type-I amino-terminal propeptide (PINP, bone formation marker). RESULTS The 24-h mean PTH concentration decreased in both genders ( P < 0·001), with maximal changes seen 6 and 12 months following GHR in men and women, respectively. Increases in 24-h mean NcAMP ( P < 0·05), calcium ( P < 0·001) and bone turnover markers ( P < 0·001) occurred in both genders following GHR, with maximal changes at 1 month in men, but at 3 months for NcAMP, calcium and CTX and 12 months for PINP in women. Maximal NcAMP increase was higher in men ( P = 0·009). CONCLUSIONS Following GHR, PTH target-organ sensitivity increased in both genders, demonstratedby simultaneous reduction in PTH concentration and increase in NcAMP, calcium and bone turnover. In women, improvement in renal PTH sensitivity was delayed and reduced, and changes in bone turnover were delayed, with increase in bone resorption preceding bone formation. Both factors may contribute to the reduced bone mineral density (BMD) response to GHR observed in women.

The Circadian Rhythm of Osteoprotegerin and Its Association with Parathyroid Hormone Secretion

“…This method has been previously validated for similar comparisons (8,41). Repeated-measures ANOVA assumes normally distributed errors, equal variances, and sphericity.…”

Effect of Oral Phosphate and Alendronate on Bone Mineral Density When Given as Adjunctive Therapy to Growth Hormone Replacement in Adult Growth Hormone Deficiency

“…The number of patients recruited to the study was determined from a power calculation performed using data from our previous studies (11,12,14,15). The SD of the mean change in PTH in our previous studies was 2.0 ng/liter.…”

“…GH replacement (GHR) in AGHD results in an increase in PTH target-organ sensitivity, as evidenced by a decrease in PTH with simultaneous increase in NcAMP, markers of bone turnover and serum adjusted calcium, and this may lead to the increase in bone turnover and BMD consistently reported after GHR (12,14,15).…”

“…Temporal fluctuations in PTH secretion are particularly important in bone remodeling (9). The nocturnal rise in PTH concentration is absent in postmenopausal osteoporotic women (9,10), and blunting of the nocturnal PTH rise has been reported in patients with untreated AGHD (11)(12)(13)(14)(15).…”

“…Patients with untreated AGHD have a reduction in the sensitivity of the kidney and bone to the effect of PTH, as evidenced by higher PTH concentration in the presence of lower nephrogenous cAMP (NcAMP; marker of PTH activity at the kidney), together with lower bone turnover markers and serum adjusted calcium concentration than healthy controls-a change that may be reflected in the reduction in bone turnover and BMD (11)(12)(13)(14)(15). GH replacement (GHR) in AGHD results in an increase in PTH target-organ sensitivity, as evidenced by a decrease in PTH with simultaneous increase in NcAMP, markers of bone turnover and serum adjusted calcium, and this may lead to the increase in bone turnover and BMD consistently reported after GHR (12,14,15).…”