Prevention of corticosteroid-induced osteoporosis: results of a patient survey.

OBJECTIVE: To evaluate the current use of bone densitometry and agents to prevent bone loss among long-term corticosteroid users. METHODS: A telephone survey of patients receiving long-term oral corticosteroid treatment. RESULTS: One hundred forty-seven patients receiving a mean prednisone dose of 10 mg per day for an average of 1-2 years were surveyed. Twenty-nine percent reported having a bone density test, 29% were taking calcium supplements, and 45% were receiving vitamin D. Forty percent of postmenopausal (PMP) women were receiving hormone replacement therapy and 14%, bisphosphonate treatment. Forty-two percent of PMP women were receiving no preventive treatment. Patients who were evaluated by primary care physicians and rheumatologists were more likely to have undergone bone density testing and to have received preventive treatments than were patients of other specialists. CONCLUSION: Many patients receive inadequate treatment to prevent corticosteroid-induced osteoporosis, and physician specialty is an important predictor of bone density testing and treatment. A broad educational effort directed to physicians of varied specialties is needed to ensure that osteoporosis prevention becomes the standard of care for patients receiving long-term corticosteroid treatment.

Metabolic studies of rat renal tubule cells loaded with cystine: the cystine dimethylester model of cystinosis.

The cause of Fanconi syndrome in cystinosis is enigmatic. It has previously been shown that renal tubules could be loaded with cystine by incubating them with cystine dimethylester (CDE), mimicking the biochemical hallmark of cystinosis. Such tubules have impaired transport, decreased whole-cell O2 consumption, and substrate utilization. In this study, the metabolic disturbances in cystine-loaded renal tubule cells were further characterized. Isolated rat renal tubules were loaded with cystine by incubating them with 2 mM CDE for 10 min. This had no significant effect on total ATPase, Na(+)-K(+)-ATPase, or the ouabain-insensitive ATPase activity of renal tissue homogenates from these cystine-loaded tubules. Intracellular K was significantly lower in the cystine-loaded tubules (37 +/- 2 versus 47 +/- 3 nEq/mg; P < 0.008). Intracellular ATP was reduced by 39% in the cystine-loaded tubules (23.7 +/- 2.4 versus 38.1 +/- 3.3 nmol/mg of protein; P < 0.0025). CDE (2 mM) reduced isolated mitochondrial O2 consumption with glutamate as the substrate by 66% (4.7 +/- 0.7 versus 13.9 +/- 0.8 nm/min per mg of protein, P < 0.001) but had no effect on mitochondrial O2 consumption with succinate as the substrate. It was speculated that the impaired transport from cystine loading with CDE is secondary to a decrease in energy generation.

Voluntary exercise increases gonadotropin secretion in male Golden hamsters.

To determine the effect of voluntary exercise and food restriction on reproductive hormone secretion, 48 adult male hamsters were placed in cages with (EX) or without (SED) running wheels. One-half of the animals in each exercise group was fed ad libitum, and the other half was food restricted to reduce their body weight to 90 g over 4 wk. After 10 wk, the EX ad libitum-fed group had much larger testes and much higher serum follicle-stimulating hormone and testosterone levels than the other three groups, but these values in the EX food-restricted hamsters were similar to those in the SED food-restricted group. In experiment 2, 20 adult male hamsters were castrated and later implanted with silicone rubber capsules containing testosterone. Two weeks after implantation of the capsules, the serum follicle-stimulating hormone levels were higher in the EX than in the SED group of testosterone-treated hamsters, but not in animals receiving blank capsules. These data suggest that exercise increases gonadotropin secretion by inhibiting the negative feedback of testosterone.

Effect of cystine loading on substrate oxidation by rat renal tubules.

Isolated rat renal tubules were loaded with cystine by incubating them with 2 mM cystine dimethylester. The oxidation of 1 mM glucose and lactate was significantly decreased after 20 and 30 min of incubation, in the cystine-loaded tubules compared with control tubules. The oxidation of 1 mM butyrate was significantly decreased after 10 and 30 min of incubation in the cystine-loaded tubules. Cystine loading decreased the oxidation of 1 mM succinate at all time points examined. The O2 consumption of renal tubules was reduced 59% with cystine loading by the addition of 2 mM cystine dimethylester, and by 37% with 1 mM cystine dimethylester. These data indicate that loading normal renal tubule cells with cystine impairs their ability to oxidize metabolic fuels. This impairment in metabolism may explain the decreased transport observed previously in cystine-loaded tubules and may have implications for the human disorder, cystinosis.

Apparent difference in the roles of spleen and lymph nodes in the pathogenesis of host-versus-graft disease in murine parent/F1 chimeras.

Host-versus-graft (HVG) disease is the often fatal immunodeficiency syndrome that can be induced in susceptible strains of mice by the perinatal inoculation of semiallogenic spleen cells. To determine the distribution and engraftment of the donor cells in the spleens and lymph nodes of RFM hosts, sequential tests were done for the presence of (T6 X RFM)F1 cells marked by their ability to form donor-specific antibodies to horseradish peroxidase (HRP) and by the T6 chromosome. Quantitation of cells with intracytoplasmic antibody that bound HRP (HRPBC) and of metaphases with the T6 marker showed that greater than 90% of donor cells were located in the hyperplastic lymph nodes. The pattern of sequential changes in numbers of HRPBC corresponded with the rise and fall in titers of antibodies to HRP. The marked differences in localization of donor cells suggested that host nodes and spleens played different roles. The lymph nodes became the main sources of donor antibodies and the principal repositories of (T6 X RFM)F1 cells capable of replication. The spleen evidently served as a major site of host resistance to engraftment. This was attributed to the ability of host cells there to inhibit selectively the proliferation of the semiallogenic donor cells. It is also proposed that counts of HRPBC measured the vigor of the HVG reaction in host spleen and lymph nodes, because the appearance of virtually all these antibody-forming cells was the result of the maturational effect of the allogenic reaction on F1 donor B memory cells.

Sensitized (T6 x RFM)F1 donor B cells contribute to hypergammaglobulinemia and to poor primary responses in RFM mice with allogenic host versus graft disease.

Experimental host versus graft (HVG) disease is the fatal immunodeficiency syndrome which is induced in susceptible strains of inbred mice by the perinatal inoculation of related F1 hybrid spleen cells. The allogenic HVG reaction results in severe T-cell depletion, but hyperplasia of B cells, of which some are F1 donor in origin. To investigate the role of F1 donor B cells in the development of hyperglobulinemia in HVG mice which respond poorly to primary antigenic challenge, antibodies to horseradish peroxidase (HRP) of (T6 x RFM)F1 donor B-cell origin were used as markers for the engraftment of primed donor B cells in RFM hosts, and as sequential measures of the allogenic reaction on them. F1 donor B cells sensitized to HRP survived different stages of the HVG reaction after inoculation on Day 1 or Day 8 after birth. Tests for the anti-HRP antibody output of RFM host cells, and engrafted HRP-primed and unprimed (T6 x RFM)F1 donor cells suggested that the hyperglobulinemia seen in HVG mice was caused principally by antigen-primed, F1 donor B cells stimulated by the allogenic effect, with or without further exposure to the antigen(s) to which the donors had been sensitized prior to transplantation. The poor primary responses were attributed to the engraftment of the many donor B cells already committed, to the immunological immaturity of the host B cells, and to the lack of T-cell help for adult unprimed F1 donor B cells. Taken together with previous work, the data also suggest that antigen-primed donor B cells were engrafted in preference to equally histoincompatible donor T cells and unprimed donor B cells.