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Biomedical subjects

N A Hamdy

Publications and source records attributed to N A Hamdy.

At least 19 recordsLinked to original sources
PubMed2001

The palliative management of skeletal metastases in prostate cancer: use of bone-seeking radionuclides and bisphosphonates.

In prostate cancer, the development of skeletal metastases is associated with a significant increase in morbidity, mainly because of severe bone pain, which eventually becomes refractory to conventional analgesia. Androgen ablation is the treatment of choice, but the majority of patients relapse within 2 to 3 years from initiation of treatment. After failure of hormone therapy, external-beam irradiation therapy is effective in the palliation of pain, but radionuclides represent an attractive and cost-effective alternative. Strontium 89 is currently the most commonly used radionuclide in the palliative management of prostate cancer metastatic to the skeleton. The rationale for the use of bisphosphonates in metastatic prostate cancer is not immediately obvious, given the predominantly osteoblastic nature of the metastatic process. The clinical use of these agents rests on a number of basic and clinical observations that provide ample evidence that, in prostate cancer, the metastatic process is associated with increased bone resorption. Evidence regarding the beneficial effects of bisphosphonates in reducing morbidity from metastatic prostate cancer is reasonably solid, although the choice of optimal bisphosphonate, mode of administration, dose, and duration of treatment must be determined in large, controlled studies before their widespread clinical use can be advocated. Available therapeutic modalities that use either radionuclides or bisphosphonates can effectively and safely be used in the palliative management of metastatic prostate cancer. Neither radionuclides nor bisphosphonates have been shown to prolong survival, but the potential of both agents to beneficially alter the metastatic process in prostate cancer is intriguing.

Bone Neoplasms↗
PubMed2001

Additional beneficial effects of alendronate in growth hormone (GH)-deficient adults with osteoporosis receiving long-term recombinant human GH replacement therapy: a randomized controlled trial.

We conducted a randomized controlled trial in osteoporotic adult GH-deficient (GHD) patients to assess whether additional treatment with a bisphosphonate would further favorably influence parameters of bone turnover and bone mineral density measurements (BMD). All patients were receiving stable recombinant human (rhGH) replacement therapy for 4 yr at the start of the study. Eighteen GHD patients with osteoporosis were randomized to continue their rhGH maintenance dose or to receive combination therapy with rhGH and alendronate for 12 months. All patients were calcium and vitamin replete, and there were no changes in calcium, vitamin D, or hormone replacement therapy for the duration of the study. At baseline there were no significant differences between the alendronate and the control group in parameters of bone turnover, BMD, or prevalence of vertebral fractures. Childhood-onset and adult-onset GHD were equally distributed between the groups, with no statistical differences in age and gender or other parameters between groups. Mean serum osteocalcin, serum bone-specific alkaline phosphatase, and urinary N-telopeptide/creatinine ratio were within the normal range at the start of the study. In the alendronate group all measured parameters of bone turnover, i.e. bone-specific alkaline phosphatase, osteocalcin, and urinary N-telopeptide/creatinine ratio, significantly decreased after 6 months, with no further decrease thereafter. No changes were observed in the control group. In the alendronate-treated patients serum bone-specific alkaline phosphatase decreased from 10.9 +/- 0.9 to 6.8 +/- 0.7 microg/L at 6 months (P < 0.001), serum osteocalcin decreased from 3.9 +/- 0.4 to 1.7 +/- 0.3 microg/L (P < 0.001), and the urinary N-telopeptide/creatinine ratio decreased from 27.3 +/- 7.0 to 6.4 +/- 0.8 nmol/mmol (P = 0.01). In this group, lumbar spine BMD significantly increased from baseline by 3.4% at 6 months (P = 0.001) and by 4.4% at 12 months (P < 0.001) of treatment, with no further significant increase between 6 and 12 months (P = 0.217). No changes in lumbar spine BMD were observed in the control group. There were no significant changes in femoral neck BMD in either group for the duration of the study. No incident vertebral or peripheral fractures were documented in either group at the end of the study. In summary, this is the first report indicating that treatment with alendronate was able to significantly increase BMD at the lumbar spine in GHD patients with osteoporosis receiving stable rhGH replacement for 4 yr. This increase was significantly greater in alendronate-treated patients than in patients maintained on rhGH. The increase in lumbar spine BMD in the alendronate-treated patients was associated with a decrease in the measured markers of bone turnover, whereas these markers did not change further in the patients maintained on rhGH. This controlled study suggests that additional treatment with alendronate in GHD patients with osteoporosis receiving stable rhGH replacement therapy is effective in increasing BMD at the lumbar spine. Further investigation is required to assess whether rhGH replacement alone or combined treatment with rhGH and alendronate is able to reduce the increased fracture risk associated with GHD.

Adult↗
PubMed2001

Strategies for management of prostate cancer-related bone pain.

Prostate cancer is one of the most common malignancies and a leading cause of cancer-related death in men worldwide. In the majority of cases, prostate cancer metastases to the skeleton, in which case cancer-related bone pain becomes a major cause of morbidity. Androgen ablation is the treatment of choice for securing regression of skeletal metastases in the majority of cases. Intermittent androgen ablation is an attractive alternative, aimed at minimising adverse effects of hormone deprivation but also potentially delaying hormone-refractoriness. The development of hormone-refractoriness is heralded by a significant increase in morbidity largely because of escalating bone pain caused by the progression of the metastatic process. Skillful use of analgesics is initially successful but eventually fails to control symptoms. Localised metastases are best treated with local radiotherapy that is rapidly effective. Over the last few years, it has become clear that therapeutic modalities using bone-seeking radionuclides or bisphosphonates have been effective in the palliation of prostate cancer-related bone pain, although not affecting survival. The main limiting factor with the use of radionuclides is bone marrow suppression, also a feature of the very late stages of prostate cancer. Bisphosphonates do not carry this disadvantage. Results of large double-blind, placebo-controlled studies should be awaited, however, before advocating the widespread use of these agents in the management of patients with prostate cancer and skeletal metastases.

Analgesics↗
PubMed2000

Bisphosphonates in the management of prostate carcinoma metastatic to the skeleton.

BACKGROUND: Prostate carcinoma metastasizes frequently to the skeleton, causing significant morbidity, particularly severe bone pain. Metastatic lesions typically are osteosclerotic, but there is experimental, histologic, and biochemical evidence of increased bone resorption. Furthermore, bone resorption rates appear to correlate with bone pain. These observations provide the rationale for the use of bisphosphonates in the management of patients with prostate carcinoma and skeletal metastases. METHODS: The authors reviewed the literature and current findings on the use of biphosphonates in the management of patients with prostate carcinoma metastatic to the skeleton. RESULTS: Compared with the large number of studies with bisphosphonates in predominantly osteolytic bone disease, there have been relatively few (mostly uncontrolled) studies in patients with prostate carcinoma. Apart from the lack of appropriate experimental models, the osteoblastic nature of the metastases and the low incidence of objectively assessed endpoints of treatment (e.g., hypercalcemia, pathologic fractures) have delayed developments. Available data, however, strongly suggest that potent bisphosphonates are efficacious in reducing skeletal morbidity in patients with prostate carcinoma. CONCLUSIONS: For the optimal management of patients with skeletal metastases from prostate carcinoma with bisphosphonates their mode of administration, the dose and duration of treatment need to be evaluated. Better understanding of the cellular and molecular mechanisms underlying bone metastases can lead to the design of improved treatment protocols with potent bisphosphonates.

Bone Neoplasms↗
PubMed2000

Effects of alendronate on bone quality and remodeling in glucocorticoid-induced osteoporosis: a histomorphometric analysis of transiliac biopsies.

Effects of alendronate (ALN) on bone quality and turnover were assessed in 88 patients (52 women and 36 men aged 22-75 years) who received long-term oral glucocorticoid exposure. Patients were randomized to receive oral placebo or alendronate 2.5, 5, or 10 mg/day for 1 year and stratified according to the duration of their prior glucocorticoid treatment. Transiliac bone biopsies were obtained for qualitative and quantitative analysis after tetracycline double-labeling at the end of 1 year of treatment. As previously reported in glucocorticoid-induced osteoporosis, low cancellous bone volume and wall thickness were noted in the placebo group as compared with normal values. Alendronate treatment was not associated with any qualitative abnormalities. Quantitative comparisons among the four treatment groups were performed after adjustment for age, gender, and steroid exposure. Alendronate did not impair mineralization at any dose as assessed by mineralization rate. Osteoid thickness (O.Th) and volume (OV/BV) were significantly lower in alendronate-treated patients, irrespective of the dose (P = 0.0003 and 0.01, respectively, for O.Th and OV/BV); however, mineral apposition rate was not altered. As anticipated, significant decreases of mineralizing surfaces (76% pooled alendronate group; P = 0.006), activation frequency (-72%; P = 0.004), and bone formation rate (-71%; P = 0.005) were also noted with alendronate treatment. No significant difference was noted between the changes observed with each dose. Absence of tetracycline label in trabecular bone was noted in approximately 4% of biopsies in placebo and alendronate-treated groups. Trabecular bone volume, parameters of microarchitecture, and resorption did not differ significantly between groups. In conclusion, alendronate treatment in patients on glucocorticoids decreased the rate of bone turnover, but did not completely suppress bone remodeling and maintained normal mineralization at all alendronate doses studied. Alendronate treatment did not influence the osteoblastic activity, which is already low in glucocorticoid-induced osteoporosis.

Adult↗
PubMed1999

Bone histomorphometric evaluation of pamidronate treatment in clinically manifest osteoporosis.

The effect of pamidronate therapy on bone histology was studied in patients with osteoporosis with at least one vertebral fracture in a randomized, double-masked, placebo-controlled, multi-center trial. Patients received pamidronate 150 mg/day or placebo in addition to calcium 500 mg/day and vitamin D3 400 IU/day. Transiliac bone biopsies were obtained before and after 1 or 2 years of treatment. Of these, 23 pairs of biopsies obtained from 14 women and 9 men (mean age +/- SD, 61.5 +/- 10 years) were of sufficient quality for histomorphometry. Histomorphometry was performed on sections stained with Goldner's trichrome, using a drawing tube and a digitizer. Urinary hydroxyproline excretion decreased significantly (p < 0.005) following pamidronate treatment, indicating a decrease in bone resorption. Osteoid volume and osteoid surface also decreased significantly in the pamidronate group (p < 0.004 and p < 0.003 respectively), consistent with a secondary decrease in bone formation. Osteoid variables did not change in the placebo-treated patients. Cortical thickness, trabecular bone volume and trabecular thickness did not change after pamidronate or placebo treatment. Wall thickness, however, showed a borderline increase following pamidronate treatment. After pamidronate, eroded surface and mineral apposition rate did not change significantly in the placebo and pamidronate groups. Mineralizing surface and activation frequency showed a borderline decrease in the placebo and pamidronate groups. The decrease in mineralization lag time was of borderline significance in the pamidronate group, corroborating the absence of any negative effect on mineralization. In conclusion, pamidronate treatment led to a decrease in bone turnover and did not interfere with bone mineralization.

Adult↗
PubMed1998

Effects of the bisphosphonate olpadronate in patients with carcinoma of the prostate metastatic to the skeleton.

Prostate cancer is predominantly associated with osteoblastic bone metastases, but an increase in bone resorption has been demonstrated consistently, both histologically and biochemically. For this reason, bisphosphonates, which effectively suppress bone resorption, have been used in patients with prostate cancer metastatic to the skeleton. We studied clinical and biochemical responses 5 days and 3 months after administration of the new, potent bisphosphonate, olpadronate, in 28 patients with prostate cancer and bone metastases. All patients received 4 mg of olpadronate intravenously daily for 5 days. No additional treatment was given to the first 12 patients, while treatment was continued with oral olpadronate 200 mg daily in the following 16 patients. Serum alkaline phosphatase (ALP) activity was elevated in 93% of the patients and was positively correlated to urinary hydroxyproline excretion (r = 0.81, p < 0.0001), suggesting a coupling between bone formation and resorption. A rapid and significant suppression of bone resorption was observed in all patients after intravenous treatment. This was sustained for 4-6 weeks in all patients, but reversed thereafter in patients not receiving oral maintenance therapy. No significant changes in serum ALP activity were observed in either group during the 3 months of follow-up. At the start of treatment all patients had severe bone pain and 82% and 36% were using NSAIDs and/or opiates, respectively. Although clinical response was not a primary objective of the study, we observed that intravenous therapy was associated with a decrease in bone pain in 76% of patients and a reduction in the use of analgesics. At 3 months this response was generally sustained only in those patients who were maintained on continuous oral therapy (p < 0.05 compared with the group treated with intravenous olpadronate only). The clinical response thus appeared to parallel the biochemical changes in bone resorption.

Administration, Oral↗
PubMed1998

Low bone mass and high incidence of fractures after successful simultaneous pancreas-kidney transplantation.

BACKGROUND: Simultaneous pancreas-kidney transplantation successfully restores normoglycaemia and corrects uraemia in insulin-dependent diabetes mellitus patients with end-stage renal failure due to diabetic nephropathy. Low bone turnover and cortical osteopenia are often associated with the diabetic state and corticosteroid-induced bone loss, predominantly trabecular, is expected post-transplantation. Little is known, however, about the resultant long-term effects of successful simultaneous pancreas-kidney transplantation on bone mass and consequent fracture rate. METHODS: We studied bone and mineral metabolism, bone densitometry (using dual X-ray absorptiometry), and fracture prevalence in a cross-sectional design in 31 IDDM patients at least 12 months (mean 40+/-23 months) after successful simultaneous pancreas-kidney transplantation. RESULTS: All patients were insulin-independent and mean creatinine clearance was 64 +/- 21 ml/min. Secondary hyperparathyroidism, probably multifactorial, was found in 55% of the patients. Increased bone turnover as suggested by elevated osteocalcin concentrations was present in 45% of the patients. Twenty-three per cent of patients had a significant decrease in bone mass (T score < -2.5 SD) at the predominantly trabecular lumbar spine sites. In contrast, 58% demonstrated a similarly low bone mass at the femoral neck, where cortical bone is prevalent. Forty-five per cent of patients had documented vertebral (mostly asymptomatic) and non-vertebral fractures. CONCLUSION: Our findings suggest that low bone mass is prevalent after successful simultaneous pancreas-kidney transplantation, and that this is associated with a high incidence of fractures, representing a cause for concern with regard to long-term morbidity. Contrary to the predominant trabecular bone loss expected with corticosteroid excess, cortical bone loss was prevalent in our patients, possibly due to pre-existing diabetic state and persistent hyperparathyroidism.

Absorptiometry, Photon↗
PubMed1998

Skeletal effects of two years of treatment with low physiological doses of recombinant human growth hormone (GH) in patients with adult-onset GH deficiency.

A low bone mass in adults with childhood-onset GH deficiency (GHD) is likely to be caused by deficient bone accretion during childhood and early adulthood, whereas a decreased bone mass in patients with adult-onset GHD is likely to be caused by an imbalance in bone remodeling. Data on bone mineral density (BMD) and biochemical parameters of bone metabolism and data on response of these parameters to treatment with GH are scarce in patients with adult-onset GHD. It has been suggested that in patients with GHD, GH at the relatively high dose originally used may have beneficial effects on the skeleton. To address the question as whether lower, more physiological doses would have similar effects on the skeleton, we studied 47 patients with adult-onset GHD (27 women and 20 men, range 26-70 yr) randomized to receive one of three recombinant human GH (rhGH) dose regimens: 0.6 IU/day, 1.2 IU/day, or 1.8 IU/day as part of a study examining optimal GH dose replacement therapy. After 24 weeks of treatment, the dose of rhGH was individually adjusted to maintain the concentration of serum insulin growth factor-I within the normal laboratory reference range. Biochemical parameters of bone metabolism were measured at baseline and after 24 and 52 weeks and 2 yr of treatment. BMD of the lumbar spine was measured at baseline and after 52 weeks and 2 yr of treatment. Parameters of bone metabolism generally fell within the low-normal range and increased in a dose-dependent manner at 24 weeks of treatment. Between 24 and 52 weeks of rhGH treatment, mean serum osteocalcin levels and alkaline phosphatase activity further increased, whereas mean 24-h urine hydroxyproline/creatinine and N-telopeptide/creatinine excretion remained unchanged. After 52 weeks of treatment, serum alkaline phosphatase activity and 24-h urine hydroxyproline/ creatinine excretion decreased, although not to pretreatment levels. Mean BMD at the lumbar spine (Z-score) was normal at baseline (-0.20 +/- 0.16) and increased during treatment (at 2 yr of treatment: 0 +/- 0.20; P < 0.005). Our data suggest that a low physiological dose of rhGH, individually adjusted to maintain serum insulin-like growth factor I levels within the normal laboratory reference range, increased bone turnover in favor of bone formation, as suggested by the significant, albeit small increase in BMD observed after 2 yr of treatment. Further studies are required to establish whether in patients with adult-onset GHD the preservation and/or increase in bone mass observed with the use of physiological doses of rhGH could be maintained with longer-term treatment.

Adult↗
PubMed1997

Long-term effects of bisphosphonates on the growing skeleton. Studies of young patients with severe osteoporosis.

Osteoporosis in children and adolescents is relatively uncommon and usually secondary to identifiable causal factors. There are no generally accepted therapies for patients with no treatable underlying cause of disease. Any treatment of young patients with bone-acting compounds should be not only effective but also devoid of adverse effects on bone growth and remodeling. For many years we have been studying the effects of bisphosphonates-an effective treatment of postmenopausal osteoporosis-on the growing skeleton. We review here our experience in the treatment of young patients with osteoporosis with special emphasis on issues of skeletal safety and effectiveness, and we discuss the available literature data. We studied 12 patients aged between 10.7 and 17.2 years with symptomatic osteoporosis and multiple fractures treated with the bisphosphonates pamidronate or olpadronate for periods between 2 and 8 years continuously. Linear growth continued normally on treatment; there was even a catch-up growth in prepubertal patients, and there was no excessive suppression of bone remodeling, assessed biochemically. Bone biopsies obtained at various stages during treatment showed bone of normal lamellar structure without mineralization defects. There was an increase in calcium balance, already evident within 10 days, the level of which was maintained for at least 3 years of treatment. This was associated with progressive increases in bone mineral density along a different slope from that of healthy peers as well as correction of vertebral deformities on X-rays in patients given bisphosphonates before puberty. Treatment was well tolerated and clinical improvement was remarkable. Our studies, supported by literature data, strongly suggest that bisphosphonate therapy can be beneficial to young patients with osteoporosis for whom no other options are currently available, and justify planning controlled studies in more common conditions for which no treatment is currently available, such as osteogenesis imperfecta.

Adolescent↗
PubMed1996

The flare in serum alkaline phosphatase activity after orchiectomy: a valuable negative prognostic index for progression-free survival in prostatic carcinoma.

PURPOSE: We determined whether an early flare in serum alkaline phosphatase activity after orchiectomy was of prognostic value for progression-free survival in patients with advanced prostatic carcinoma. MATERIALS AND METHODS: A retrospective analysis of a data base from a Dutch multicenter study on prostatic carcinoma was done to determine the prognostic value of a flare in alkaline phosphatase activity after orchiectomy in 112 patients with metastatic (75%) or locally advanced (25%) disease. Cox's proportional hazards models and Kaplan-Meier survival curves were used. RESULTS: Of the patients 50% had initially increased alkaline phosphatase levels and a flare in activity was demonstrated in 87% 2 to 4 weeks after orchiectomy. The prostate specific antigen nadir (cutoff 4 ng./ml.) 6 months after orchiectomy was of significant prognostic value for progression-free survival. A flare in alkaline phosphatase activity after orchiectomy demonstrated an early significant prognostic value for progression-free survival, independent of the serum alkaline phosphatase activity. CONCLUSIONS: The simplicity, ready availability and cost-effectiveness of serum alkaline phosphatase activity as a prognostic index render it attractive to the clinician, particularly early in the course of prostatic carcinoma. Measuring the flare in alkaline phosphatase activity within 1 month of orchiectomy may permit early identification of patients in whom the disease is likely to progress rapidly and who would potentially benefit from aggressive treatment.

Aged↗
PubMed1995

Effect of alfacalcidol on natural course of renal bone disease in mild to moderate renal failure.

OBJECTIVE: To determine whether alfacalcidol--used in management of overt renal bone disease--may safely prevent renal bone disease when used earlier in course of renal failure. DESIGN: Double blind, prospective, randomised, placebo controlled study. SETTING: 17 nephrology centres from Belgium, France, the Netherlands, and the United Kingdom. SUBJECTS: 176 patients aged 18-81 with mild to moderate chronic renal failure (creatinine clearance 15-50 ml/min) and with no clinical, biochemical, or radiographic evidence of bone disease. INTERVENTIONS: Alfacalcidol 0.25 micrograms (titrated according to serum calcium concentration) or placebo given for two years. MAIN OUTCOME MEASURES: Quantitative histology of bone to assess efficacy of treatment and renal function to assess safety. RESULTS: 132 patients had histological evidence of bone disease at start of study. Biochemical, radiographic, and histological indices of bone metabolism were similar for the 89 patients given alfacalcidol and the 87 controls given placebo. After treatment, mean serum alkaline phosphatase activity and intact parathyroid hormone concentration had increased by 13% and 126% respectively in controls but had not changed in patients given alfacalcidol (P < 0.001). Hypercalcaemic episodes occurred in 10 patients given alfacalcidol (but responded to decreases in drug dose) and in three controls. Histological indices of bone turnover significantly improved in patients given alfacalcidol and significantly deteriorated in controls: among patients with abnormal bone histology before treatment, bone disease resolved in 23 (42%) of those given alfacalcidol compared with two (4%) of the controls (P < 0.001). There was no difference in rate of progression of renal failure between the two groups. CONCLUSION: Early administration of alfacalcidol can safely and beneficially alter the natural course of renal bone disease in patients with mild to moderate renal failure.

Adolescent↗
PubMed1995

Clinical characteristics of a population of dyslexic children in Assiut, Egypt.

Two groups of pupils from special tract learning schools were randomly selected for this study. The first group (55 pupils) fulfilled the World Federation of Neurology (WFN) definition of developmental dyslexia (DD). The second group (retarded readers, RR) included 20 pupils with IQs between 80 and 90. A group of normal readers was randomly selected from the 5 school grades as a control group. This study showed that the performance IQ of the DD group was not only higher than the verbal IQ, but the DD group also had superior performance IQ compared to normal readers. In the arithmetic achievement test, both DD and RR groups had nearly similar total scores, which were significantly lower than that of the control group. None of the arithmetic subtests could differentiate between DD and RR groups. In linguistic achievement tests, only spontaneous writing and oral spelling could differentiate subjects with DD from the RR group.

Adult↗
PubMed1995

Skeletal metabolism in patients with osteoporosis after discontinuation of long-term treatment with oral pamidronate.

Bisphosphonates are used with increasing frequency in the treatment of patients with osteoporosis. Continuous administration of low doses of nitrogen-containing bisphosphonates by mouth is the preferred mode of therapy. The skeletal half-life of bisphosphonates is long, however, and little is known about their long term effects on skeletal metabolism. We examined the changes in biochemical parameters of bone turnover [serum alkaline phosphatase and urinary hydroxyproline (OHP)], in bone mineral density, and in fracture frequency after discontinuation of long term (mean, 6.5 yr, range, 5-9 yr) therapy with oral pamidronate (150 mg/day) in 30 patients with osteoporosis and vertebral fractures. Serum alkaline phosphatase and urinary OHP were significantly lower at the end of long term treatment (90% and 72% of basal values, respectively). Serum alkaline phosphatase had increased to basal values within 6 months of stopping treatment, whereas OHP increased significantly to a maximum average of 92% of pretreatment values. There was no change in the every 6-month bone mineral density measurements of the lumbar spine and the femoral neck during the 2 yr after stopping treatment. Spine fracture index, calculated by the method of Raymakers and co-workers, was 0.83 +/- 0.12 before treatment, 0.85 +/- 0.12 at the end of treatment, and 0.85 +/- 0.13 2 yr after stopping treatment (nonsignificant). There was also no significant change in the rate of new vertebral fractures on or up to 2 yr after stopping treatment (48.5 of 1000 and 46.5 of 1000 patient yr, respectively). Our data demonstrate that the sustained suppression of bone turnover induced by long term treatment with pamidronate is readily reversible on stopping treatment. The beneficial effect of this treatment regimen on the skeleton, however, appears to be maintained for at least 2 yr after discontinuation of treatment.

Administration, Oral↗
PubMed1995

Recovery of serum calcium concentrations following acute hypocalcemia in patients with osteoporosis on long-term oral therapy with the bisphosphonate pamidronate.

Bisphosphonates, synthetic compounds that are taken up preferentially by the skeleton and that suppress bone resorption, are currently used in the management of patients with osteoporosis. Long-term uninterrupted administration of low oral doses is the preferred mode of treatment in current clinical trials with newer bisphosphonates. These compounds have, however, a long residence time in the skeleton, and there is no information about their long-term effects on blood calcium homeostasis. We examined the effect of long-term therapy with oral bisphosphonate on blood calcium homeostasis following an acute hypocalcemic stimulus. Twenty patients with vertebral osteoporosis (10 untreated controls and 10 treated with oral pamidronate, 150 mg/day for at least 5 yr) were given intravenous infusions of sodium EDTA, and the concentrations of calcium and PTH in blood were followed for 24 h. Serum calcium concentrations decreased similarly in both groups (maximum decrease 0.21 mmol/L and 0.22 mmol/L, respectively). The recovery of serum calcium concentrations was identical in both groups, and all patients had normal concentrations at 24 h. Plasma PTH increased to a peak of 17.3 +/- 2.5 pmol/L in the control group and to 17.0 +/- 3.1 pmol/L in the pamidronate-treated patients. During the whole study period, there was no difference in either the peak PTH response or in the recovery of plasma PTH values between the two groups. However, when only PTH responses between 60 min and 24 h were examined, there were differences between the two groups. Plasma PTH values, although strictly within the normal range, were significantly higher in the pamidronate-treated patients (P = 0.001). There were no differences in the calcemic responses during this period. Further, there were no detectable changes in immunoreactive PTH-related protein in either group after the EDTA infusions. In conclusion, our study showed that longterm therapy with oral pamidronate does not affect the calcemic response to an acute hypocalcemic stimulus in patients with osteoporosis.

Acute Disease↗