Effects Of Pamidronate Research Articles

Effect of low dose pamidronate in the treatment of thalassemia-induced osteoporosis

Introduction: Thalassemia is the most common genetic defect, globally affecting about 200 million individuals. Increased longevity in transfusion-dependent thalassemia patients is accompanied by complications such as osteopenia, osteoporosis and skeletal disabilities. In this regard, increased bone reabsorption in beta-thalassemia has led to the administration of bisphosphonates for these patients. Objectives: Although there is growing consensus on the effectiveness of pamidronate in thalassemia osteoporosis, the findings about the dosage and duration of pamidronate are inconsistent. Accordingly, the present study aimed to assess the impact of low-dose pamidronate on the bone mineral density (BMD) of major beta-thalassemia patients. Patients and Methods: In this study, the participants encompassed 20 transfusion-dependent major thalassemia patients with Z-score< -2.5 in bone mineral densitometry. Bone density was determined in the lumbar vertebras and hip by using dual X-ray absorptiometry. Pamidronate was administered intravenously in monthly dosage of 1 mg/kg over six months. Results: According to the findings, the participants’ mean age was 16.55±3.15 years (Range: 10-25 years). The baseline mean of Z-score for lumbar vertebras was -2.92±1.14 and reached -1.95±1.2 after six months (P<0.001). Moreover, the baseline mean of Z-score for the hip region was -2.00 (0.65) and reached -1.55 (0.77). Conclusion: The dosages of 1 mg/kg over six months had a statistically significant effect on bone density and improved Z-scores of lumbar vertebrae and hip bone density by 45% and 20%, respectively.

Continuing Relief of Pain with Long Term Treatment for Osteoporosis with Intravenous Pamidronate

Purpose: Bisphosphonates are valuable in reducing the incidence of fracture. Side effects limit persistence with oral therapy and long term studies of pain relief are difficult to pursue. Intravenous bisphosphonates offer an alternative treatment to oral bisphosphonates and are tolerated over a longer period. The use of Pamidronate, an intravenously administered bisphosphonate, to benefit pain and reduce fracture incidence in the long term has not been extensively investigated. The study aimed to investigate the effect of Pamidronate on pain, vertebral fracture incidence and Bone Mineral Density over 6 or more years.Methods: Patients were offered intravenous Pamidronate if oral treatment with bisphosphonates or Hormone replacement therapy had failed due to side effects, fractures continued on oral treatment or oesophageal reflux led to cessation of oral treatment. Pain was assessed using the Nottingham health profile; radiographs were used to evaluate vertebral fracture and DXA measured bone mineral density.Results: The primary outcome was the pain domain. Median patient follow up was 9 years. Pain had improved significantly (p = 0.03) and in 68% pain had either improved or remained unchanged. Vertebral fractures occurred in 14% of patients in the first 3 years, 9.5% in years 4-6, but increased in years 7-9 to 27%. Bone mineral density increased in the lumbar spine (p < 0.001) but not at the femoral neck.Conclusions: Pamidronate had a beneficial effect on pain over the period of the study. Vertebral fracture incidence increased after 6 years of Pamidronate, although spine BMD increased significantly.

Anti-resorptive effect of pamidronate on extraction socket wall in dogs.

The aim of this experimental in vivo investigation was to assess the anti-resorptive effect of low concentration pamidronate on the buccal plate in fresh extraction sockets. The distal roots of the third premolars were extracted bilaterally in six dogs. A collagen matrix loaded with either pamidronate (test group) or saline (control group) was positioned on the outer surface of buccal bone immediately after tooth extraction and subsequently covered with a coronally advanced flap. Histological and histomorphometric outcomes were evaluated 12weeks later. The mean vertical distance between the buccal and lingual bone crest differed significantly between the test and control groups (0.52±0.43 and 2.21±1.15mm, respectively; p=.037). The width of the buccal bone 1mm below the crest was significantly wider in the test group than the control group (4.68±0.68 vs. 3.44±0.60mm, p<.001). Local application of pamidronate onto a collagen matrix may reduce the dimensional changes of the buccal bone plate both vertically and horizontally.

The Bisphosphonate Pamidronate is an Intestinal Antiinflammatory Agent in Rat and Mouse Experimental Colitis.

Statins have antiinflammatory effects at the cardiovascular level because of inhibition of prenylation, which also probably underlies their therapeutic effects in preclinical models of inflammatory bowel disease. Another inhibitor of prenylation, namely alendronate, reduces colitis in rodents. In this study, we aim to explore the therapeutic potential of second-generation, nitrogen-containing bisphosphonates in 3 preclinical models of colitis. The trinitrobenzenesulfonic acid and dextran sulfate sodium models of rat colitis and the adoptive lymphocyte transfer model of colitis in mice were used. Pamidronate, alendronate, and ibandronate were tested. Treatments were administered in equimolar doses through the oral or intraperitoneal route. The effect of pamidronate on prenylation and cytokine release was assessed in vivo and in vitro. Pretreatment with pamidronate, but not with ibandronate or alendronate, improves chemically induced trinitrobenzenesulfonic acid and dextran sulfate sodium colitis in rats. Moreover, this beneficial effect is extended to lymphocyte transfer colitis. Pamidronate has no effect on intestinal epithelial cells in vitro in terms of cytokine/chemokine release, but enhances IFN-γ, IL-6, and IL-10 production by T cells in coculture. Pamidronate also exerts a direct immunomodulatory effect on T cells, favoring Th1 differentiation and impairing Th17 polarization. Pamidronate presents antiinflammatory and immunomodulatory properties in 3 different models of experimental colitis in rodents. This effect requires oral administration and may involve T cells in the gut mucosa, although the exact mechanism is unclear.

Does pamidronate enhance the osteogenesis in mesenchymal stem cells derived from fibrous hamartoma in congenital pseudarthrosis of the tibia?

Neurofibromatosis type 1 (NF1) is a commonly occurring genetic disorder in children. Mutation in the NF1 gene has its implication in poor osteoblastic capabilities. We hypothesised that pamidronate will enhance the osteoblastic potential of the mesenchymal stem cells (MSCs) derived from lipofibromatosis tissue of children with congenital pseudarthrosis tibia (CPT) associated with NF1. In this study, bone marrow MSCs (BM MSCs) and CPT MSCs were obtained from three patients undergoing salvage surgeries/bone grafting (healthy controls) and those undergoing excision of the hamartoma and corrective surgeries respectively. The effects of pamidronate (0, 10nM, 100nM and 1μM) on cell proliferation, toxicity and differentiation potential were assessed and the outcome was measured by staining and gene expression. Our outcome showed that CPT MSCs had more proliferation rate as compared to BM MSCs. All 3 doses of pamidronate did not cause any toxicity to the cells in both the groups. The CPT MSCs showed less differentiation with pamidronate compared to the healthy control MSCs. This was quantitated by staining and gene expression analysis. Therefore, supplementation with pamidronate alone will not aid in bone formation in patients diagnosed with CPT. An additional stimulus is required to enhance bone formation.

Effects of Pamidronate on Dental Enamel Formation Assessed by Light Microscopy, Energy-Dispersive X-Ray Analysis, Scanning Electron Microscopy, and Microhardness Testing

The aim of the present work was to investigate birefringence and morphology of the secretory-stage enamel organic extracellular matrix (EOECM), and structural and mechanical properties of mature enamel of upper incisors from adult rats that had been treated with pamidronate disodium (0.5 mg/kg/week for 56 days), using transmitted polarizing and bright-field light microscopies (TPLM and BFLM), energy-dispersive X-ray (EDX) analysis, scanning electron microscopy (SEM) and microhardness testing. BFLM showed no morphological changes of the EOECM in pamidronate and control groups, but TPLM revealed a statistically significant reduction in optical retardation values of birefringence brightness of pamidronate-treated rats when compared with control animals (p0.05). The present study indicates that pamidronate can affect birefringence of the secretory-stage EOECM, which does not seem to be associated with significant changes in morphological and/or mechanical properties of mature enamel.

Effects of Pamidronate in Acute Cardiotoxicity Induced by Doxorubicin in Rats

AimEvaluate pamidronate (Pam) effects in ventricular function, matrix metalloproteinase‐2 (MMP‐2) activity, oxidative stress, and myocardial energetic metabolism during acute doxorubicin (Dox)‐induced cardiotoxicity.Methods64 Wistar rats were allocated in 4 groups: Control, Dox, Pam and Dox + Pam. Rats received Pam (3 mg/kg, IP) or saline. After 24 hours, rats received Dox (20 mg/kg, IP) or saline. Forty‐eight hours after Dox injection, rats were euthanized. Statistical analysis: two‐way ANOVA.ResultsDox induced diastolic and systolic ventricular dysfunction and increased MMP‐2 activity. Dox increased myocardial oxidative stress (increased in lipid hydroperoxide, and decreased in catalase, superoxide dismutase and glutathione peroxidase myocardial levels) and impaired myocardial energetic metabolism (increased in phosphofructokinase and decreased in β‐hydroxyacyl dehydrogenase myocardial levels). Pam associated with Dox did not change ventricular function or MMP‐2 activity, but it decreased lipid hydroperoxide (p=0.042) and increased catalase (p&lt;0.001) and superoxide dismutase levels (p&lt;0.001). Also, Pam improved phosphofructokinase (p=0.021) and β‐hydroxyacyl dehydrogenase levels (p&lt;0.001).ConclusionPam attenuated acute Dox‐induced cardiotoxicity because it decreased oxidative stress and modulated myocardial energetic metabolism.Acknowledgement: PROPe‐UNESP and FAPESP.

Pamidronate effects in horse osteoarthritis: Relationship of clinical score with inflammatory biomarkers in synovial fluid

Introduction: The use of pamidronate in horses with OA could prevent resorptive phenomena associated with joint disease, and may reduce the inflammatory process and resulting pain. Objective was to analyze differences in clinical scores in horses with osteoarthritis before and after the treatment with pamidronate and standardized correlation with the protein profile and inflammatory markers (IL-6, TNF-α, MMP-2 and MMP-9).Materials and methods: Inflammation markers of synovial fluid from clinically healthy horses (clinical score ≤ 4), and patients (n = 5) (clinical score N 5–9) were evaluated basal and days 3, 10 and 21 after treatment. On day 0 and day 2 intravenous pamidronate (90 mg) were applied to the sick horses. IL-6 and TNF-α were assessed by ELISA; MMP-2 and 9 were evaluated by zymography. Changes in synovial fluid protein profile of pre and post treatment were evaluated by SDS-PAGE. Direct BP inhibition on MMP-9 activity in vitro was determined by zymography. Results: IL-6 did not show significant difference, TNF-α; increased at day 21 post treatment, differences were observed between healthy group and “day 3” (p b 0.001) and “untreated patients” (p b 0.01). For MMP-2 p= ns and MMP-9 showed significant individual differences after the second dose And in protein profile study, before and after treatment, no significant differences were observed. Conclusion: Pamidronate reduced MMP-9 activity. Protease was involved in the degenerative and inflammatory processes by degrading the extracellular matrix, but no direct inhibition on MMP-9 occurred. For TNF-α, the increased may be associated with a certain exacerbation of the inflammatory process which can be considered as beneficial to the resolution of chronic arthritis.

Clinical efficacy and safety of pamidronate therapy on bone mass density in early post-renal transplant period: a meta-analysis of randomized controlled trials.

IntroductionThe overall effect of pamidronate on bone mass density (BMD) in the early renal transplant period varies considerably among studies. The effects of pamidronate on graft function have not been determined.Materials and MethodsA comprehensive search was conducted in PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL) and Embase independently by two authors. Randomized controlled trials of pamidronate evaluating bone loss in the first year of renal transplantation were included. Methods reported in the “Cochrane Handbook for Systematic Reviews of Interventions 5.0.2” were used to evaluate changes of lumbar spine and femoral neck BMD, and serum creatinine, calcium and intact parathyroid hormone (iPTH) levels. Fixed or random effect models were used as appropriate.ResultsSix randomized trials evaluating 281 patients were identified. One hundred forty-four were treated with pamidronate and 137 were control patients. Administration of pamidronate was associated with significant reduction of bone loss in the lumbar spine, compared to the control group (standardized mean difference (SMD) = 24.62 [16.25, 32.99]). There was no difference between the pamidronate treated and control femoral neck BMD (SMD = 3.53 [−1.84, 8.90]). A significant increase in the serum creatinine level of the intervention group was seen, compared to the control group. The serum calcium and iPTH of the pamidronate and control groups were not different after 1 year (serum creatinine: SMD = −3.101 [−5.33, −0.89]; serum calcium: SMD = 2.18 [−0.8, 5.16]; serum iPTH: SMD = 0.06 [−0.19, 0.31]). Heterogeneity was low for serum calcium and iPTH and high for serum creatinine.ConclusionsThis meta-analysis demonstrated the beneficial clinical efficacy of pamidronate on BMD with no association with any alteration in graft function during the first year of renal transplantation. Significant heterogeneity precludes the conclusion of the relationship between serum creatinine and pamidronate.

Effect of bisphosphonates on the rapidly growing male murine skeleton.

Bisphosphonates are effective for preventing and treating skeletal disorders associated with hyperresorption. Their safety and efficacy has been studied in adults where the growth plate is fused and there is no longitudinal bone growth and little appositional growth. Although bisphosphonate use in the pediatric population was pioneered for compassionate use in the treatment of osteogenesis imperfecta, they are being increasingly used for the treatment and prevention of bone loss in children at risk of hyperresorptive bone loss. However, the effect of these agents on the growing skeleton in disorders other than osteogenesis imperfecta has not been systematically compared. Studies were, therefore, undertaken to examine the consequences of bisphosphonate administration on the growth plate and skeletal microarchitecture during a period of rapid growth. C57Bl6/J male mice were treated from 18 to 38 days of age with vehicle, alendronate, pamidronate, zoledronate, or clodronate at doses selected to replicate those used in humans. Treatment with alendronate, pamidronate, and zoledronate, but not clodronate, led to a decrease in the number of chondrocytes per column in the hypertrophic chondrocyte layer. This was not associated with altered hypertrophic chondrocyte apoptosis or vascular invasion at the growth plate. The effects of pamidronate on trabecular microarchitecture were less beneficial than those of alendronate and zoledronate. Pamidronate did not increase cortical thickness or cortical area/total area relative to control mice. These studies suggest that bisphosphonate administration does not adversely affect skeletal growth. Long-term investigations are required to determine whether the differences observed among the agents examined impact biomechanical integrity of the growing skeleton.

Bisphosphonate treatment in non-ambulatory patients with spastic quadriplegic cerebral palsy and other neuromuscular disorders: effectiveness of pamidronate vs zoledronic acid

Searchable abstracts of presentations at key conferences on calcified tissues ISSN 2052-1219 (online)

Effects of Pamidronate and Calcitriol on the Set Point of the Parathyroid Gland in Postmenopausal Hemodialysis Patients with Secondary Hyperparathyroidism

Background/Aims: Secondary hyperparathyroidism may worsen after the administration of pamidronate in postmenopausal hemodialysis (HD) patients. The aim of this study was to evaluate the short-term effect of coadministration of calcitriol and pamidronate on dynamic parathyroid hormone (PTH) secretion. Methods: Fifteen postmenopausal women undergoing regular HD with serum intact PTH levels of >200 pg/ml were enrolled. The PTH-ionized calcium (iCa) curve was evaluated by the response to hypo- and hypercalcemia induced with 1 and 4 mEq/l of dialysate calcium, respectively. Parameters were compared after pamidronate was administered and after coadministration of pamidronate and calcitriol. Changes in serum levels of maximal serum PTH (PTH_max), basal PTH (PTH_base) and minimal PTH (PTH_min) were evaluated. Results: Pamidronate therapy resulted in a decrease in predialysis basal plasma iCa (p < 0.05) and an increase in PTH_max (p < 0.01), PTH_base (p < 0.01) and PTH_min (p < 0.01). The change in serum iCa and PTH was reversed after the coadministration of calcitriol and pamidronate. Conclusion: Our study demonstrated that pamidronate therapy is associated with a reduced plasma iCa and increased PTH secretion. These adverse effects may be reversed by calcitriol. These findings suggest that in considering pamidronate treatment in postmenopausal patients with osteoporosis receiving HD, it might be safer to add calcitriol to prevent the increased PTH secretion.

In Silico Investigations of the Anti-Catabolic Effects of Pamidronate and Denosumab on Multiple Myeloma-Induced Bone Disease

It is unclear whether the new anti-catabolic agent denosumab represents a viable alternative to the widely used anti-catabolic agent pamidronate in the treatment of Multiple Myeloma (MM)-induced bone disease. This lack of clarity primarily stems from the lack of sufficient clinical investigations, which are costly and time consuming. However, in silico investigations require less time and expense, suggesting that they may be a useful complement to traditional clinical investigations. In this paper, we aim to (i) develop integrated computational models that are suitable for investigating the effects of pamidronate and denosumab on MM-induced bone disease and (ii) evaluate the responses to pamidronate and denosumab treatments using these integrated models. To achieve these goals, pharmacokinetic models of pamidronate and denosumab are first developed and then calibrated and validated using different clinical datasets. Next, the integrated computational models are developed by incorporating the simulated transient concentrations of pamidronate and denosumab and simulations of their actions on the MM-bone compartment into the previously proposed MM-bone model. These integrated models are further calibrated and validated by different clinical datasets so that they are suitable to be applied to investigate the responses to the pamidronate and denosumab treatments. Finally, these responses are evaluated by quantifying the bone volume, bone turnover, and MM-cell density. This evaluation identifies four denosumab regimes that potentially produce an overall improved bone-related response compared with the recommended pamidronate regime. This in silico investigation supports the idea that denosumab represents an appropriate alternative to pamidronate in the treatment of MM-induced bone disease.

Letter to the Editor: Acute Effects of Intravenous Administration of Pamidronate in Patients with Osteoporosis

To the Editor: We read the interesting article Acute Effects of Intravenous Administration of Pamidronate in Patients with Osteoporosis in the Journal of Korean Medical Science by Lim et al. (1). We would like to comment and compare these data to a study recently published by our research group (2). The two studies had different initial aims, but still they share the same results in determining the modulatory effect of inflammation of aminobisphosphonates, such as pamidronate. The pamidronate belongs to the family of aminobisphosphonates (N-BPs), currently the major class of drugs used for the treatment of osteoporosis and other diseases characterized by increased bone resorption. The immune modulation exerted by pamidronate has not yet fully been understood (3). In vitro experiments have shown an anti-inflammatory effect of this N-BP; (4, 5) as well as a pro-inflammatory one (6, 7). Moreover contrasting results were obtained when pamidronate was used for the treatment of different inflammatory or immunologic diseases, such as rheumatoid arthritis (8, 9) or systemic sclerosis. The aminobiphosphonates act on farnesylpyrophosphate synthase (FPPS) and inhibit the mevalonate pathway, the latter being responsible for production of cholesterol and isoprenoid lipids. In particular we can hypothesize that the inflammatory phenotype is due to lack of enzymes downstream the FPPS, and in particular the lack of geranylgeranyl-pyrophosphate (GGPP) could be associated to the activation of caspase-1 and the high IL-1β release. Lim et al. (1) emphasized that in vivo infusion of pamidronate at a therapeutic dose of 30 mg increased production of two inflammatory cytokines, IL-6 and TNF-α in serum. The increase is an acute effect after intravenous injection (1). Recently, our group demonstrated that pamidronate is able to increase the sensitivity to bacterial compounds both in the murine macrophagic cell line (Raw 264.7) and in Balb/c mice, by an incremental release of IL1β. These findings are in agreement with published data concerning inflammatory modulation in alendronate treated-mice (2). Moreover the effect of pamidronate does not depend on its concentration, whereas it may be involved in the increase of susceptibility to pro-inflammatory compounds such as muramildipeptide or lipopolysaccaride (2). In summary, we agree with the study by Lim et al. (1) and we emphasize the pivotal role of pamidronate in the modulation of inflammatory response. Sincerely.

Spinal involvement in chronic recurrent multifocal osteomyelitis (CRMO) in childhood and effect of pamidronate

There are only a few studies that address the frequency and type of spinal involvement in patients with chronic recurrent multifocal osteomyelitis (CRMO) as well as the outcome of these patients treated with pamidronate (PAM). We performed a retrospective study on patients with CRMO and analyzed clinical and pain assessments as well as regional and whole body MRI findings and compared with posttreatment findings. Of 102 children and adolescents with CRMO, 27 (26%) had involvement of the spine. Vertebral deformities were seen in 14 of these 27 patients, scoliosis or kyphosis in 6. After routine whole body MRI, 19 complained of back pain, whereas eight were asymptomatic with spinal lesions detected incidentally. A total of 72 spinal lesions were detected, thoracic vertebrae being the most commonly affected. Seven patients were treated with PAM; all of whom had vertebral deformities and ongoing back pain. Pain resolution was achieved within 3 months of PAM treatment in every case. One patient subsequently developed a pain amplification syndrome. Repeat MRI performed at a mean interval of 13 months revealed partial or complete resolution of vertebral hyperintensities in every patient. Improvement of vertebral height was seen in a total of three vertebrae in two patients. Severe side effects were not observed. In conclusion, we demonstrated that spinal involvement and associated vertebral deformities with or without kyphoscoliosis are not rare in CRMO, and PAM appears to be an effective and safe treatment for this condition. Although controlled studies are urgently needed, the use of PAM for refractory CRMO with extended spinal involvement (vertebral deformities, kyphosis, and scoliosis) should be considered, especially after failing of conventional therapy.

Protein kinase C is inhibited by bisphosphonates in prostate cancer PC-3 cells

Bisphosphonates are expected to be effective at preventing tumor metastasis to bone tissue. Since protein kinase C (PKC) plays a crucial role in cancer progression, we examined the effect of bisphosphonates on PKC expression to clarify the mechanism behind the inhibition of the bone metastasis of prostate cancer by bisphosphonates. We found that pamidronate inhibits PKC protein expression and PKC activity in prostate cancer PC-3 cells. PKC protein expression was markedly reduced by treatment with 100 microM of pamidronate. The inhibitory effect of PKC expression by pamidronate was specific for PKCalpha and PKCzeta. Nitrogen-containing bisphosphonates are known to inhibit the mevalonate pathway, but the effect of pamidronate on PKC expression was not due to the inhibition of this pathway. Urokinase-type plasminogen activator (uPA) is one of the critical proteins in tumor metastasis and decreased in bisphosphonate-treated PC-3 cells. We also showed that uPA expression was suppressed by PKC inhibitors (calphostin C and staurosporine) and induced by a PKC activator (PMA) in PC-3 cells, suggesting that the inhibition of uPA by bisphosphonates is involved in PKC inhibition. This is the first finding that bisphosphonates suppress PKC expression in cancer cells. These results strongly suggest that one of the mechanisms behind the inhibitory effect of bisphosphonates on tumor bone metastasis is mediated by PKC inhibition.

Long-Term Effects of Pamidronate in Thalassemic Patients with Severe Bone Mineral Density Deficits

Osteoporosis is a common complication in thalassemia major (TM). Our previous study demonstrated severe bone mineral density (BMD) deficits at spine and hip in 62 and 35% of TM patients. This study assessed the effects of different treatments (calcium, vitamin D and bisphosphonate) on patients' BMD, which was measured at baseline and after 3-year treatments by dual energy X-ray absorptiometry (DEXA). Twenty-one untreated patients, 11 patients on calcium/vitamin D and seven patients on additional pamidronate, were recruited. They were comparable for gender (p = 0.630) and serum ferritin levels (p = 0.412). The median BMD Z-scores at lumbar spine and left hip improved only in patients with standard plus pamidronate treatments (baseline: −3.01 and −3.05, end-of-study: −2.12 and −2.09; p = 0.018 and 0.028, respectively). In contrast, BMD Z-scores at hip worsened in untreated patients (p = 0.034). In conclusion, long-term improvement in BMD in TM patients was observed with bisphosphonate but not calcium and vitamin D treatment.

Effect of Pamidronate on Bone Loss After Kidney Transplantation: A Randomized Trial

Kidney transplantation is associated with an increased risk of bone fracture and rapid loss of bone mineral density after kidney transplantation. Randomized controlled trial. Patients were randomly assigned to treatment (n = 46) or control (no treatment; n = 47) groups. Patients were stratified according to parathyroid hormone level and sex. Those with parathyroid hormone level less than 150 pg/mL were excluded. The treatment and control groups received pamidronate, 1 mg/kg, perioperatively and then at 1, 4, 8, and 12 months or no treatment, respectively. All received calcium (500 mg) and vitamin D (400 units) daily. Immunosuppression was cyclosporine and prednisolone, with no difference in dosing between the 2 groups. Bone mineral density was evaluated by means of dual-energy x-ray absorptiometry of the lumbar spine and hip at baseline and 3, 6, 12, and 24 months, with the primary end point at 1 year of percentage of change in bone mineral density from baseline. Clinical fractures were recorded and also evaluated by means of spinal radiographs at baseline and 1 and 2 years. Pamidronate protected bone mineral density at the lumbar spine; bone mineral density increased by 2.1% in the treatment group and decreased by 5.7% in the control group at 12 months (P = 0.001). Protection was also seen in Ward's area of the hip (P = 0.002) and the total hip (P = 0.004). There was no difference in femoral neck bone mineral density loss between the 2 groups. Fracture rates in the treatment and control groups were 3.3% and 6.4% per annum, respectively. This study was not powered to detect differences in fracture rates. Pamidronate protects against posttransplantation bone loss at the lumbar spine and Ward's area of the hip.

Pharmacotherapy with Pamidronate Disodium of Osteolytic Bone Metastases of Breast Cancer, Osteolytic Lesions of Multiple Myeloma, and Paget's Disease

High bone turnover disorders are characterized by excessive osteoclastic activity resulting in loss of bone mass and quality, fractures, deformities, debilitating pain, loss of mobility and hypercalcemia. These complications have a major impact in quality of life, and control of osteoclast activity is critical to reduce or prevent these skeletal events. Over the last 2 decades bisphosphonates became an integral part of the management of these disorders. Bisphosphonates, analogues of pyrophosphate, bind to hydroxyapatite crystals and have a very high affinity for bone mineral. Their retention in bone and rapid clearance from the circulation make them safe and effective agents for inhibition of osteoclast activity. Pamidronate is one such bisphosphonate that has been effective in treating Paget's disease, myeloma bone disease and osteolytic bone metastases from breast cancer. This review will focus on the effects of pamidronate in these disorders.

Osteopenia–Osteoporosis Syndrome in Patients with Thalassemia: Understanding of Type of Bone Disease and Response to Treatment

With increased life expectancy, thalassaemic bone disease including osteopenia osteoporosis syndrome (OOS) is a major cause of bone pain and fragility fractures especially of the lumbar spine, which may be found in 70–80% adult patients with β-thalassaemia worldwide, accounting for significant bone morbidity. The causes of OOS in thalassaemia syndromes are multifactorial, and the exact treatment is far from ideal. We undertook a prospective study of 34 thalassaemic patients to evaluate the effect of pamidronate and hormone replacement therapy (if hypogonadal) on bone quantity by DXA scan quality by histomorphometry of bone biopsy and bone dynamics by biochemical markers of bone turnover.Our results show that all patients had osteopenia with abnormal bones on histomorphometry before commencement of treatment. Thalassaemia major patients had high turnover bone disease and all responded favourably to treatment whereas intermedia patients had low turnover bone disease and responded poorly to treatment. Our data also showed that ICTP and PICP is a discriminatory test but histomorphometry is the only test for characterisation of bone morphology.