It has been postulated that secondary hyperparathyroidism contributes to bone loss and the high incidence of hip fractures in the elderly population, but there are no data on serum intact parathyroid hormone concentrations in these patients. In this study, serum intact parathyroid hormone (PTH) levels have been measured in 39 elderly patients with hip fracture; in addition, serum 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3 concentrations have been measured. Twenty patients (51.3%) had elevated serum intact PTH concentrations whilst five (12.8%) had abnormally low serum 25-hydroxyvitamin D3 levels and serum 1,25-dihydroxyvitamin D3 was reduced in only two. These results provide the first direct evidence for secondary hyperparathyroidism in elderly patients with hip fracture. Vitamin D deficiency is unlikely to be the sole cause of secondary hyperparathyroidism in these subjects and calcium deficiency by itself may also contribute.

SUMMARY. Glomerular filtration rate (GFR) is frequently reduced in elder1 -Rople. However, the effect of this on mineral metabolism in this population has recr3ved little attention. GFR, serum intact parathyroid hormone (PTH) and vitamin D mdabolites , were measured in 37 patients admitted to hospital for various reasons. In 20 patier>:--wirli GFR > 50 mL/min, an elevated serum intact PTH concentration (> 5 . 4 pmol/L) was found in two, while in 17 patients with GFR < 50 mL/min PTH was elevated in 13. One of this group was hypercalcaemic and presumed to have primary hyperparathyroidism. Adjusted calcium was normal in all other patients. Two patients had a low serum 25-hydroxyvitamin D concentration (< 9 nmol/L) suggesting vitamin D insufficiency while a further five had a reduced 1,25-dihydroxyvitamin D concentration, four of these having a GFR < 50 mL/min. We conclude that hyperparathyroidism is common in hospitalized elderly patients, particularly in those with mild to moderate renal insufficiency. This may contribute to bone mineral loss in such patients. Additional key phrases: glomerular filtration rate; intact parathyroid hormone; 2s-hydroxyvitamin D; 1,2S-dihydroxyvitamin DAbnormalities of bone and mineral metabolism are an almost inevitable consequence of renal failure. Secondary hyperparathyroidism, which undoubtedly contributes to these abnormalities, occurs early in the course of chronic renal insufficiency and may result from decreased calcium absorption as a consequence of reduced renal synthesis of 1,25-dihydroxyvitamin D (1,25(OH),D). However, because of the frequent absence of specific symptoms, relatively few data have appeared on calciotropic hormone levels in patients with mild to moderate renal impairment. I Glomerular filtration rate (GFR) decreases with age2 and elderly patients may thus provide a population on whom to study biochemical markers of calcium and bone metabolism in mild renal insufficiency. Moreover, ageing itself has important effects on bone homeostasis. Everyone loses bone with ageing, though in women the rate of loss is greater than in men.' The factors responsible for the loss of cortical and trabecular bone It is well established that parathyroid hormone (PTH) is a key regulator of 1,25(OH),D synthesis which ultimately regulates calcium absorption. Responsiveness within this regulatory pathway appears to become impaired in elderly osteoporotic patient^.^ There have been reports that serum PTH levels increase with age,6s7 which could result from functional impairment of the ageing kidney or could reflect altered vitamin D metabolism.* However, previous studies have involved the use of assays of PTH which recognize carboxy-terminal hormone fragments. Though known to accumulate in renal insuffi~iency,~ such fragments are of no known biological significance and do not reflect parathyroid secretory activity. In contrast, assays recognizing the amino terminal segment of the PTH moleculelo have suitable specificity in biological terms but lack the sensitivity needed to detect sm...

The binding and cellular processing of NH2-terminal parathyroid (PTH) hormone by confluent monolayers of opossum kidney (OK) cells was characterized using radiolabeled PTH peptide analogues. Time- and temperature-dependent specific binding of 125I-labeled (Nle-8,18, Tyr-34)-NH2-bovine(b)PTH-(1-34) was accompanied by the appearance of degraded radiolabel in the cell medium. Degrading activity was observed to be a specific consequence of binding by PTH receptors. Degrading activity was inhibited by monensin, chloroquine, and NH4+ but not by chymotrypsin inhibitors. Acid washing demonstrated that greater than 80% of total cell-associated specific binding at equilibrium was located in a rapidly internalized (acid-resistant) pool. Monensin pretreatment led to increased acid-resistant binding, presumably through inhibition of turnover of internalized receptor ligand and indicated that the degradation of radiolabel was probably associated with processing of the receptor-ligand complex. Release of intact radiolabel from the acid-resistant pool indicated that some of the internalized peptide was recycled out of the cell in an undegraded form (retroendocytosis). Acid-resistant binding and degradation of 125I-(Nle-8,18, Tyr-34)-NH2-bPTH-(3-34) was minimal, indicating that this ligand was not internalized. It is concluded that the binding and internalization of PTH-(1-34) fragment by confluent OK cells is a specific receptor-mediated process. Cellular processing of PTH-(1-34) conforms to established models of internalization by receptor-mediated endocytosis.

The measurement of parathyroid hormone (PTH) is important in the investigation of disorders of mineral metabolism. Though the first immunoassay for PTH was described more than 25 years ago, it is only recently that methods have been developed which provide the required sensitivity and specificity to detect small changes in hormone secretion in normal subjects. These new methods take advantage of modern labelled antibody technology and have already been shown capable of yielding improvements in the diagnosis and monitoring of disorders which involve changes in PTH secretion. In addition, they are now providing fresh insight into the basic physiology of PTH secretion.

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