Intestinal Absorption of Calcium in Greyhounds: The Response to Intermittent and Continuous Administration of Human Synthetic Parathyroid Hormone Fragment 1–34 (Hpth 1–34)

Abstract

Long-term studies of gastrointestinal radio-calcium absorption were undertaken in adult greyhounds before and during two treatment regimes with human parathyroid hormone fragment 1-34 (hPTH 1-34). The results were correlated with plasma vitamin D metabolite levels and kinetic indices related to the balance of fluxes of calcium between plasma and the rapidly exchangeable calcium pools of bone. Compared with adult man, results obtained before treatment started showed lower indices of gastrointestinal calcium absorption and considerably higher concentrations of 24-hydroxycalcidiol in the dogs. Daily injections of hPTH 1-34 at 1.7 microgram day-1 kg-1 significantly increased indices of radiocalcium absorption and plasma calcitriol concentrations, while only causing transient calcaemic responses. The individual magnitudes of the calcaemic response correlated positively with indices of radiocalcium retention in the exchangeable pools of bone which in turn correlated positively with 'late-phase' absorption of radiocalcium from the gut. Subcutaneous infusions of hPTH 1-34 at 0.5 microgram day-1 kg-1 to the same dogs were just insufficient to cause hypercalcaemia, but increased plasma calcitriol concentrations. Indices of radiocalcium absorption were not increased. Continuous parathyroid hormone (PTH) infusion is now known to substantially down-regulate renal PTH receptor density, whereas recovery after a brief exposure to PTH occurs within 24 h. It is possible that the differences in response of the gut to the two regimes may in part be related to their differing effects on some PTH receptors.

Periodic courses of human 1–34 parathyroid peptide alternating with calcitriol paradoxically reduce bone remodelling in spinal osteoporosis

“…Further experience has confirmed that this trend is statistically highly significant [5]; and similar results were seen in normal greyhounds given the same treatment [6]. However, when given in this way alone, in contrast to our findings in dogs [7], hPTH 1-34 did not increase dietary calcium absorption in the patients [4,8] and may have mediated a transfer of bone mineral from the peripheral to the axial skeleton [9]. It also gave rise to an increase in indices of bone resorption, as well as bone formation, in both iliac trabecular bone and in the skeleton as a whole.…”

Parathyroid Hormone‐like Bioactivity in Tumours From Patients With Oncogenic Osteomalacia

“…It is known that some peptide hormones stimulate when administered in an episodic fashion but are inhibitory when administered continuously (Belchetz et a/., 1978). The effect of exogenous hPTH 1-34 on human and canine renal 1 a-hydroxylase has been shown to be dependent on the mode of administration (Podbesek et al, 1984;Slovik et a/., 1984). While there is some evidence that amino-terminal PTH is secreted in a pulsatile manner (Segre, 1983) there are currently no data concerning the pattern of release of humoral material in hypercalcaemia of malignancy and oncogenic osteomalacia.…”

The Biological Enhancement of Spinal Fusion for Spinal Degenerative Disease

“…It has been well known that the continuous infusion of PTH1-34 is associated with a catabolic effect, but that an intermittent administration promotes an anabolic effect on bone [52,53,54]. The mechanism underlying the anabolic and catabolic effect of PTH1-34 on bone metabolism is still unclear.…”