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Urinary excretion of pyridinium cross-links is one of the biochemical markers for bone resorption in metabolic bone diseases. Efficacy of immunoassay for deoxypyridinoline (D-pyr) for monitoring effects of antiresorptive therapy was evaluated in 44 women with osteoporosis, including 4 patients with asymptomatic primary hyperparathyroidism. Urinary free forms and protein-bound (conjugated) forms of D-pyr were measured totally by a modified enzyme-liked immunoabsorbent assay (ELISA; PYRILINKS-DTM, Metra Biosystem, Mountain View, CA, USA), which required prehydrolysis of urine samples and adequate acidity adjusted with alkali. There was a close relationship between total excretion of D-pyr measured by reverse-phase high performance liquid chromatography (HPLC) and that measured by ELISA. In 27 patients, the percent change of urinary D-pyr by ELISA following hormone replacement therapy (HRT) was similar to that of urinary total forms of D-pyr using HPLC at the end of the first third, and sixth month. In 8 patients whose series of urine samples were corrected following HRT, the percent change of urinary total excretion of D-pyr by ELISA at the end of the third month was approximately −40%, significantly greater than that of excretion of free forms of D-pyr measured by ELISA (−30%;P

Gut transit using radiopaque markers was assessed in 5 healthy subjects and 24 diabetic patients. In the diabetics, various parameters including duration of the disease and diabetic complications, such as neuropathy, retinopathy and nephropathy, were determined, and the relationships between gut transit times and these complications were evaluated. The effect of cisapride on gut transit was studied in 10 diabetic patients. Large intestinal, descending colon, distal colon, and whole gut transit times were delayed in diabetics with autonomic neuropathy compared to controls and to diabetics without autonomic neuropathy (P less than 0.01). There was no difference in proximal colon transit times among them. An inverse correlation was observed between CVRR and the transit times for descending colon, distal colon, large intestine and whole gut. Large intestinal and whole-gut transit times were delayed in diabetics with retinopathy or with nephropathy compared to diabetics without those complications (P less than 0.01). In the diabetics, oral administration of 7.5 mg/day of cisapride for 2 weeks significantly accelerated descending colon transit (P less than 0.05) and partially accelerated distal colon, large intestinal and whole-gut transit. It is concluded that diabetics with autonomic neuropathy have delayed transits for the whole gut and that this finding is apparent to some extent in the distal colon but not in the proximal colon. Chronic oral administration of cisapride, a gastrointestinal prokinetic drug, was effective to improve these gastrointestinal motility disorders in diabetics with autonomic neuropathy.

Several in vivo experiments have revealed that a synthesized fluorinated analogue of vitamin D, 26,26,26,27,27,27-hexafluoro-1,25-dihydroxyvitamin D3 (26,27-F6-1,25(OH)2D3) has a higher and longer-lasting biological activity than 1,25(OH)2D3 in calcium regulating actions. We evaluated the biological potency and the availability for clinical use of this compound in hypocalcemia associated with hypoparathyroidism. In an experimental setting, daily administration of 650 pmol/kg of 26,27-F6-1,25(OH)2D3 showed an equivalent effect to that of 3250 pmol/kg of 1,25(OH)2D3 in elevating whole blood ionized calcium levels in parathyroidectomized rats. Furthermore, an additional clinical study demonstrated that 0.5-1.5 micrograms/day of 26,27-F6-1,25(OH)2D3 were considered adequate maintenance doses in various types of hypoparathyroidism and that changes of medication to the same doses of 1,25(OH)2D3 resulted in prompt decline of urinary calcium excretion and of whole blood ionized calcium levels, and in recurrence of symptoms related to hypocalcemia. Although the mechanism responsible for the high potency of this analogue remains unclear, our experience confirms that 26,27-F6-1,25(OH)2D3 has higher biological activities in bone calcium mobilization and is more potent than 1,25(OH)2D3 in correcting hypocalcemia of hypoparathyroidism in a hospital setting.

Total body bone mineral content and bone mineral content in various body sites were measured by dual-photon absorptiometry in 103 patients with non-insulin-dependent diabetes mellitus (NIDDM) and the findings were compared with those for 214 non-diabetic control subjects matched for age and body weight. Neither total body bone mineral content (TBBM) nor the bone mineral density of the third lumbar vertebra (L3 BMD) in the diabetic subjects differed from the values in control subjects of either sex, but the values were significantly decreased in patients diseased for at least five years when compared with control subjects. Regional bone mineral measurement showed prominent bone loss in the truncal site, but no reduction in bone mass was found in the head, pelvis, arms, or legs in either male or female patients. These results suggest that reduced TBBM and L3 BMD are associated with duration of the disease and that a site-specific bone defect is present in NIDDM.