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Bisphosphonate Therapy (bisphosphonate + therapy)
Kinds of Bisphosphonate Therapy Selected AbstractsIntravenous Bisphosphonate Therapy Increases Radial Width in Adults With Osteogenesis Imperfecta,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 8 2005Davide Gatti Abstract Neridronate therapy in adult patients with OI significantly increases the cross-sectional area of the proximal radius. This observation may provide an additional explanation for the antifracture efficacy of bisphosphonates. Introduction: Bisphosphonate therapy decreases by 70-90% the fracture risk in patients with osteogenesis imperfecta (OI). This decrease is somewhat greater than that expected from the BMD changes, supporting the hypothesis that bisphosphonate therapy is associated with structural changes, not detectable by BMD measurements. Materials and Methods: To explore this hypothesis, pQCT measurements at the nondominant radius were obtained in a group of adult OI patients participating in a randomized clinical trial with neridronate. Results: The total volumetric BMD of the ultradistal radius rose significantly in patients treated with neridronate and calcium + vitamin D (neridronate group) compared with patients treated with calcium + vitamin D alone (control group). No significant differences were observed in trabecular BMD and in volumetric cortical density in either group. In the neridronate group, the cross-sectional area rose significantly versus both baseline values and the control group. These latter changes were associated with ,20% increases in bending breaking resistance index (BBRI). Conclusion: Our observation, if extended to postmenopausal osteoporosis, may provide a new explanation for the fracture risk reduction observed in osteoporotic patients treated with bisphosphonates. [source] Treatment of Idiopathic Hyperphosphatasia With Intensive Bisphosphonate TherapyJOURNAL OF BONE AND MINERAL RESEARCH, Issue 5 2004Tim Cundy MD Abstract In a family with IH, a rare high turnover bone disease, two older siblings were wheelchair-bound with severe skeletal deformity by age 15. Their youngest affected sibling was treated intensively with intravenous bisphosphonates for 3 years. The treatment was well tolerated and prevented the development of deformity and disability. Introduction: Idiopathic hyperphosphatasia (IH, also known as juvenile Paget's disease) is a rare genetic bone disease characterized by very high bone turnover and progressive bony deformity. Inhibitors of bone resorption have been used to suppress bone turnover in the short term, but there is no published data on long-term efficacy. Materials and Methods: An 11-year-old girl with IH, who had two severely affected older siblings, presented with progressive deformity and deafness and long bone fractures. Conventional pediatric doses of pamidronate had failed to prevent clinical deterioration or suppress bone turnover completely. Intensive bisphosphonate therapy (frequent 5-mg ibandronate infusions) was given to try and arrest progression of the skeletal disease. Growth and development, pure tone audiometry, biochemistry, radiology, densitometry (DXA), and bone histology were monitored. Results: A total of 45 mg ibandronate was given over 3 years until skeletal maturity was reached (20, 15, and 10 mg for years 1,3, respectively). Ibandronate treatment was well tolerated, and biochemical markers of bone turnover suppressed to within the age-appropriate normal range There was some progression of her thoracic kyphosis, but she had no further fractures and remained mobile and active at an age when her siblings had become wheelchair-bound. A significant recovery of hearing (p < 0.01) was documented, particularly at low frequencies. Radiographs showed improvement in spinal osteoporosis and cortical bone dimensions and arrest of progressive acetabular protrusion. Areal bone density increased substantially (lumbar spine z-score from ,2.2 to + 1.8). Tetracycline-labeled bone biopsy specimens were taken before and after 18 months of intensive treatment. The second biopsy showed suppression of bone turnover and a doubling of trabecular thickness, with no mineralization defect, and no osteopetrosis. Conclusions: Intensive bisphosphonate treatment prevented the development of deformity and disability and improved hearing in this child with IH. The dose of bisphosphonate, which is substantially greater than is usually used in pediatric bone disease, had no adverse effects, in particular on bone mineralization. [source] Implant Placement in Patients with Oral Bisphosphonate Therapy: A Case SeriesCLINICAL IMPLANT DENTISTRY AND RELATED RESEARCH, Issue 3 2010Ghasem Omati Shabestari DDS ABSTRACT Background: Although the effect of bisphosphonates on dental implant osseointegration is not clear, dental implant failures attributable to oral bisphosphonate therapy have been reported in patients with osteoporosis. Purpose: The aim of this study was to evaluate implant survival in patients with a history of bisphosphonate therapy in a retrospective survey. Materials and Methods: A total of 46 ITI implants placed in 21 osteoporotic patients (females; average age 53 years, range 42,79 years) were evaluated with regard to probing depth, mobility, thread exposure, and bleeding on probing. All patients were under oral bisphosphonate therapy. Results: None of implants showed mobility and all patients could be considered free from peri-implantitis. Time of bisphosphonate therapy before and after implant insertion showed no statistically significant influence on PD, BOP, and TE. Likewise, implant location, prosthetic type, and opposing dentition had no statistically significant influence on the clinical and radiological parameters of implants. Conclusion: Within the limitations of this study, it could be concluded that neither being on oral bisphosphonate treatment before implant placement nor starting bisphosphonate therapy after implant installation might jeopardize the successful osseointegration and clinical and radiographic condition of the implants. [source] Oral sodium clodronate induced osteonecrosis of the jaw in a patient with myelomaEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 1 2007Amir H Montazeri Abstract Bisphosphonate therapy has been shown to significantly reduce the incidence of skeletal complications in patients with myeloma. Several recent reports have described osteonecrosis of the jaw (ONJ) associated with bisphosphonates. These reports mainly demonstrate an association between ONJ and potent i.v. bisphosphonates. We report a case of ONJ in a patient with myeloma, who had only been treated with oral sodium clodronate. While the degree of risk for osteonecrosis in patients taking oral bisphosphonates, such as clodronate, remains uncertain it would be prudent to consider carefully the indications for the use of these agents to minimise the risk of ONJ. [source] Retention, Distribution, and Effects of Intraosseously Administered Ibandronate in the Infarcted Femoral Head,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 1 2007James Aya-ay Abstract The local distribution, retention, and effects of intraosseous administration of ibandronate in the infarcted femoral heads were studied. Intraosseous administration effectively delivered and distributed ibandronate in the infarcted femoral heads and decreased the femoral head deformity in a large animal model of Legg-Calve-Perthes disease. Introduction: Bisphosphonate therapy has gained significant attention for the treatment of ischemic osteonecrosis of the femoral head (IOFH) because of its ability to inhibit osteoclastic bone resorption, which has been shown to contribute to the pathogenesis of femoral head deformity. Because IOFH is a localized condition, there is a need to explore the therapeutic potential of local, intraosseous administration of bisphosphonate to prevent the femoral head deformity. The purpose of this study was to investigate the distribution, retention, and effects of intraosseous administration of ibandronate in the infarcted head. Materials and Methods: IOFH was surgically induced in the right femoral head of 27 piglets. One week later, a second operation was performed to inject 14C-labeled or unlabeled ibandronate directly into the infarcted head. 14C-ibandronate injected heads were assessed after 48 h, 3 weeks, or 7 weeks later to determine the distribution and retention of the drug using autoradiography and liquid scintillation analysis. Femoral heads injected with unlabeled ibandronate were assessed at 7 weeks to determine the degree of deformity using radiography and histomorphometry. Results: Autoradiography showed that 14C-Ibandronate was widely distributed in three of the four heads examined at 48 h after the injection. Liquid scintillation analysis showed that most of the drug was retained in the injected head, and almost negligible amount of radioactivity was present in the bone and organs elsewhere at 48 h. At 3 and 7 weeks, 50% and 30% of the 14C-drug were found to be retained in the infarcted heads, respectively. Radiographic and histomorphometric assessments showed significantly better preservation of the infarcted heads treated with intraosseous administration of ibandronate compared with saline (p < 0.001). Conclusions: This study provides for the first time the evidence that local intraosseous administration is an effective route to deliver and distribute ibandronate in the infarcted femoral head to preserve the femoral head structure after ischemic osteonecrosis. In a localized ischemic condition such as IOFH, local administration of bisphosphonate may be preferable to oral or systemic administration because it minimizes the distribution of the drug to the rest of the skeleton and bypasses the need for having a restored blood flow to the infarcted head for the delivery of the drug. [source] Effect of pamidronate on bone turnover and implant migration after total hip arthroplasty: A randomized trialJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 1 2005J. Mark Wilkinson Abstract In this trial we studied the effect of pamidronate on periprosthetic bone turnover and pelvic implant migration over 2 years after hybrid total hip arthroplasty (THA). Twenty-two patients received 90 mg of pamidronate and 22 received placebo at randomization 5 days after surgery. Rapid periprosthetic bone loss occurred in the placebo group over the first 6 months and was accompanied by transient increases in biochemical markers of bone turnover. Partial recovery in bone mass occurred in most region after this period. No recovery of bone mass occurred at the femoral calcar or the medical wall of the acetabulum. Femoral calcar bone loss at 2 years was strongly predicted by acute biomarker changes at week 6. Pamidronate therapy reduced femoral bone loss in the region of the femoral calcar (P=0.01), but did not affect pelvic bone loss. Pamidronate therapy also inhibited the transient rise in biochemical markers of bone turnover during this period. Pamidronate therapy did not affect acetabular cup migration. Cup migration was inversely related to subject age, but unrelated to initial post-operative bone mineral density, or subsequent bone loss. In summary, early periprosthetic bone loss is associated with a transient expansion of the bone remodeling space. Bisphosphonate therapy reduces femoral calcar bone loss and bone turnover after THA, but did not influence cup migration in this study. Acute changes in biochemical markers predict femoral periprosthetic bone loss. © 2004 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved. [source] Bisphosphonate therapy for patients with breast carcinomaCANCER, Issue S3 2003Who to treat, when to stop Abstract Bisphosphonates have become well established in the treatment of patients with metastatic bone disease, although the optimal use of these agents has not been defined clearly. Randomized, controlled trials have demonstrated that treatment with intravenous pamidronate can significantly reduce the rate of skeletal-related events in patients with bone metastases from myeloma or advanced breast carcinoma. To date, there are few data from controlled, randomized studies to support the use of bisphosphonates in patients with bone metastases from malignancies other than breast carcinoma and myeloma. The optimal duration of treatment is unknown. Recent data have demonstrated that prolonged treatment is tolerated well, with no obvious toxicity. Generally, treatment is continued irrespective of the development of skeletal-related events and until there is a substantial decline in performance status. The widespread use of bisphosphonates will have major financial implications. Retrospective studies have suggested that the cost-effectiveness ratio is high for patients with advanced breast carcinoma. These ratios may be improved by targeting therapy to patients at high risk of developing complications from skeletal metastatic disease. Among patients with skeletal metastases from breast carcinoma, a recent retrospective analysis demonstrated that patients with disease confined to the skeleton were at greater risk of pathologic fractures compared with patients who had additional extraosseous disease. It is interesting to note that approximately two-thirds of patients with advanced breast carcinoma in the randomized trials of intravenous pamidronate had disease confined to the skeleton. The use of markers of bone turnover to identify patients who are most likely to benefit from bisphosphonate therapy or to identify patients who will respond to such therapy is the subject of further investigation. There are conflicting data on the use of bisphosphonates as an adjuvant therapy. Currently, such treatment should occur only as part of a clinical trial. Bisphosphonates can be used to prevent bone loss as a result of therapy for malignant disease, e.g., premature menopause in patients with early breast carcinoma. Cancer 2003;97(3 Suppl):854,8. © 2003 American Cancer Society. DOI 10.1002/cncr.11146 [source] Long-Term Protective Effects of Zoledronic Acid on Cancellous and Cortical Bone in the Ovariectomized Rat,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 4 2008Jürg A Gasser PhD Abstract Current bisphosphonate therapies effectively prevent bone loss in postmenopausal women. We studied the effect of a single intravenous dose of ZOL in ovariectomized rats. Protection from bone loss was dose dependent, lasting for up to 32 weeks, supporting the rationale for an annual intravenous dosing regimen of ZOL for treatment of postmenopausal osteoporosis. Introduction: Once-yearly dosing with zoledronic acid (ZOL) 5 mg can increase BMD and reduce fracture rate in postmenopausal women with low BMD. The primary objective of this study was to determine the duration of bone protective effects of a single dose of ZOL in ovariectomized rats, an animal model of postmenopausal osteopenia. Secondary objectives were to determine the effects on bone turnover and mechanical properties. Materials and Methods: Female Wistar rats (10 per group) received single intravenous doses of ZOL 0.8, 4, 20, 100, or 500 ,g/kg, alendronate 200 ,g/kg, or isotonic saline 4 days before bilateral ovariectomy. Sham-operated controls were pretreated with saline. Mass and density of cancellous and cortical bone (pQCT) were measured at 4-wk intervals for 32 wk. Bone architecture (,CT), bone formation dynamics (fluorochrome label-based histomorphometry), and biomechanical strength in compression testing were also assessed at 32 wk. Results: Ovariectomy-associated BMD loss was significantly attenuated for 32 wk by ZOL ,4 ,g/kg for total BMD, ZOL ,20 ,g/kg for cortical BMD, and ZOL ,4 ,g/kg for cancellous BMD (p < 0.01 versus ovariectomized controls). Alendronate 200 ,g/kg was of equivalent potency to ZOL 20 ,g/kg. Ovariectomy-associated decreases in trabecular architectural parameters were dose-dependently attenuated by ZOL. Alendronate 200 ,g/kg was equivalent to ZOL 20 ,g/kg. The bone resorption marker TRACP5b indicated transient suppression of elevated osteoclast activity by ZOL relative to OVX-rats even at the lowest dose of 0.8 ,g/kg, whereas at 100,500 ,g/kg, the effect was significant relative to the OVX control for the entire duration of the study of 32 wk. Bone formation parameters were not significantly affected by ZOL 20 ,g/kg but were significantly reduced by ZOL 100,500 ,g/kg. Alendronate 200 ,g/kg was equivalent to ZOL 100 ,g/kg. ZOL produced dose-related improvements in bone strength parameters after ovariectomy. Alendronate 200 ,g/kg was of similar potency to ZOL 20 ,g/kg. Conclusions: The duration and magnitude of the bone-protecting effect of a single intravenous dose of ZOL in ovariectomized rats is dose dependent and lasts for up to 32 wk. Compared with alendronate, ZOL shows 10-fold higher potency in preventing bone loss. These data support the use of an annual intravenous ZOL dosing regimen for the treatment of osteoporosis. [source] Atrial fibrillation and bisphosphonate therapyJOURNAL OF BONE AND MINERAL RESEARCH, Issue 1 2010Michael Pazianas Abstract Bisphosphonates are the most commonly used treatment for osteoporosis and have proven efficacy in the reduction of vertebral and nonvertebral fractures. Recently, concerns have been raised about a possible association between bisphosphonate therapy and atrial fibrillation (AF) following the report of a significant increase in risk of serious AF in women treated with zoledronic acid in the HORIZON study. Subsequent studies have produced conflicting results but have not excluded the possibility of such an association. Currently there is no direct evidence that bisphosphonates exert either acute or chronic effects on cardiac electrophysiology. Nevertheless, altered intracellular electrolyte homeostasis and proinflammatory, profibrotic, and antiangiogenic effects provide potential mechanisms by which atrial conduction could be affected in patients treated with bisphosphonates. In studies in which an increase in risk of AF has been identified, there is no evidence that this translates into increased mortality or increased risk of stroke, and the risk-benefit balance of bisphosphonate therapy in patients with osteoporosis and other forms of metabolic bone disease remains strongly positive. © 2010 American Society for Bone and Mineral Research [source] Benefit of Adherence With Bisphosphonates Depends on Age and Fracture Type: Results From an Analysis of 101,038 New Bisphosphonate Users,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 9 2008Jeffrey R Curtis Abstract The relationship between high adherence to oral bisphosphonates and the risk of different types of fractures has not been well studied among adults of different ages. Using claims data from a large U.S. health care organization, we quantified adherence after initiating bisphosphonate therapy using the medication possession ratio (MPR) and identified fractures. Cox proportional hazards models were used to evaluate the rate of fracture among nonadherent persons (MPR < 50%) compared with highly adherent persons (MPR , 80%) across several age strata and a variety of types of clinical fractures. In conjunction with fracture incidence rates among the nonadherent, these estimates were used to compute the number needed to treat with high adherence to prevent one fracture, by age and fracture type. Among 101,038 new bisphosphonate users, the proportion of persons with high adherence at 1, 2, and 3 yr was 44%, 39%, and 35%, respectively. Among 65- to 78-yr-old persons with a physician diagnosis of osteoporosis, the crude and adjusted rate of hip fracture among the nonadherent was 1.96 (95% CI, 1.48,2.60) and 1.74 (95% CI, 1.30,2.31), respectively, resulting in a number needed to treat with high adherence to prevent one hip fracture of 107. The impact of high adherence was substantially less for other types of fractures and for younger persons. Analysis of adherence in a non,time-dependent fashion artifactually magnified differences in fracture rates between adherent and nonadherent persons. The antifracture effectiveness associated with high adherence to oral bisphosphonates varied substantially by age and fracture type. These results provide estimates of absolute fracture effectiveness across age subgroups and fracture types that have been minimally evaluated in clinical trials and may be useful for future cost-effectiveness studies. [source] Bisphosphonate-Associated Osteonecrosis of the Jaw: Report of a Task Force of the American Society for Bone and Mineral Research,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 10 2007Sundeep Khosla (Chair) Abstract ONJ has been increasingly suspected to be a potential complication of bisphosphonate therapy in recent years. Thus, the ASBMR leadership appointed a multidisciplinary task force to address key questions related to case definition, epidemiology, risk factors, diagnostic imaging, clinical management, and future areas for research related to the disorder. This report summarizes the findings and recommendations of the task force. Introduction: The increasing recognition that use of bisphosphonates may be associated with osteonecrosis of the jaw (ONJ) led the leadership of the American Society for Bone and Mineral Research (ASBMR) to appoint a task force to address a number of key questions related to this disorder. Materials and Methods: A multidisciplinary expert group reviewed all pertinent published data on bisphosphonate-associated ONJ. Food and Drug Administration drug adverse event reports were also reviewed. Results and Conclusions: A case definition was developed so that subsequent studies could report on the same condition. The task force defined ONJ as the presence of exposed bone in the maxillofacial region that did not heal within 8 wk after identification by a health care provider. Based on review of both published and unpublished data, the risk of ONJ associated with oral bisphosphonate therapy for osteoporosis seems to be low, estimated between 1 in 10,000 and <1 in 100,000 patient-treatment years. However, the task force recognized that information on incidence of ONJ is rapidly evolving and that the true incidence may be higher. The risk of ONJ in patients with cancer treated with high doses of intravenous bisphosphonates is clearly higher, in the range of 1,10 per 100 patients (depending on duration of therapy). In the future, improved diagnostic imaging modalities, such as optical coherence tomography or MRI combined with contrast agents and the manipulation of image planes, may identify patients at preclinical or early stages of the disease. Management is largely supportive. A research agenda aimed at filling the considerable gaps in knowledge regarding this disorder was also outlined. [source] Juvenile Paget's Disease: The Second Reported, Oldest Patient Is Homozygous for the TNFRSF11B "Balkan" Mutation (966_969delTGACinsCTT), Which Elevates Circulating Immunoreactive Osteoprotegerin Levels,,§¶JOURNAL OF BONE AND MINERAL RESEARCH, Issue 6 2007Michael P Whyte MD Abstract The oldest person (60 yr) with juvenile Paget's disease is homozygous for the TNFRSF11B mutation 966_969delTGACinsCTT. Elevated circulating levels of immunoreactive OPG and soluble RANKL accompany this genetic defect that truncates the OPG monomer, preventing formation of OPG homodimers. Introduction: Juvenile Paget's disease (JPD), a rare autosomal recessive disorder, features skeletal pain, fracture, and deformity from extremely rapid bone turnover. Deafness and sometimes retinopathy also occur. Most patients have diminished osteoprotegerin (OPG) inhibition of osteoclastogenesis caused by homozygous loss-of-function defects in TNFRSF11B, the gene that encodes OPG. Circulating immunoreactive OPG (iOPG) is undetectable with complete deletion of TNFRSF11B but normal with a 3-bp in-frame deletion. Materials and Methods: We summarize the clinical course of a 60-yr-old Greek man who is the second reported, oldest JPD patient, including his response to two decades of bisphosphonate therapy. Mutation analysis involved sequencing all exons and adjacent mRNA splice sites of TNFRSF11B. Over the past 4 yr, we used ELISAs to quantitate his serum iOPG and soluble RANKL (sRANKL) levels. Results: Our patient suffered progressive deafness and became legally blind, although elevated markers of bone turnover have been normal for 6 yr. He carries the same homozygous mutation in TNFRSF11B (966_969delTGACinsCTT) reported in a seemingly unrelated Greek boy and Croatian man who also have relatively mild JPD. This frame-shift deletes 79 carboxyterminal amino acids from the OPG monomer, including a cysteine residue necessary for homodimerization. Nevertheless, serum iOPG and sRANKL levels are persistently elevated. Conclusions: Homozygosity for the TNFRSF11B "Balkan" mutation (966_969delTGACinsCTT) causes JPD in the second reported, oldest patient. Elevated circulating iOPG and sRANKL levels complement evidence that this deletion/insertion omits a cysteine residue at the carboxyterminus needed for OPG homodimerization. [source] Intravenous Bisphosphonate Therapy Increases Radial Width in Adults With Osteogenesis Imperfecta,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 8 2005Davide Gatti Abstract Neridronate therapy in adult patients with OI significantly increases the cross-sectional area of the proximal radius. This observation may provide an additional explanation for the antifracture efficacy of bisphosphonates. Introduction: Bisphosphonate therapy decreases by 70-90% the fracture risk in patients with osteogenesis imperfecta (OI). This decrease is somewhat greater than that expected from the BMD changes, supporting the hypothesis that bisphosphonate therapy is associated with structural changes, not detectable by BMD measurements. Materials and Methods: To explore this hypothesis, pQCT measurements at the nondominant radius were obtained in a group of adult OI patients participating in a randomized clinical trial with neridronate. Results: The total volumetric BMD of the ultradistal radius rose significantly in patients treated with neridronate and calcium + vitamin D (neridronate group) compared with patients treated with calcium + vitamin D alone (control group). No significant differences were observed in trabecular BMD and in volumetric cortical density in either group. In the neridronate group, the cross-sectional area rose significantly versus both baseline values and the control group. These latter changes were associated with ,20% increases in bending breaking resistance index (BBRI). Conclusion: Our observation, if extended to postmenopausal osteoporosis, may provide a new explanation for the fracture risk reduction observed in osteoporotic patients treated with bisphosphonates. [source] Treatment of Idiopathic Hyperphosphatasia With Intensive Bisphosphonate TherapyJOURNAL OF BONE AND MINERAL RESEARCH, Issue 5 2004Tim Cundy MD Abstract In a family with IH, a rare high turnover bone disease, two older siblings were wheelchair-bound with severe skeletal deformity by age 15. Their youngest affected sibling was treated intensively with intravenous bisphosphonates for 3 years. The treatment was well tolerated and prevented the development of deformity and disability. Introduction: Idiopathic hyperphosphatasia (IH, also known as juvenile Paget's disease) is a rare genetic bone disease characterized by very high bone turnover and progressive bony deformity. Inhibitors of bone resorption have been used to suppress bone turnover in the short term, but there is no published data on long-term efficacy. Materials and Methods: An 11-year-old girl with IH, who had two severely affected older siblings, presented with progressive deformity and deafness and long bone fractures. Conventional pediatric doses of pamidronate had failed to prevent clinical deterioration or suppress bone turnover completely. Intensive bisphosphonate therapy (frequent 5-mg ibandronate infusions) was given to try and arrest progression of the skeletal disease. Growth and development, pure tone audiometry, biochemistry, radiology, densitometry (DXA), and bone histology were monitored. Results: A total of 45 mg ibandronate was given over 3 years until skeletal maturity was reached (20, 15, and 10 mg for years 1,3, respectively). Ibandronate treatment was well tolerated, and biochemical markers of bone turnover suppressed to within the age-appropriate normal range There was some progression of her thoracic kyphosis, but she had no further fractures and remained mobile and active at an age when her siblings had become wheelchair-bound. A significant recovery of hearing (p < 0.01) was documented, particularly at low frequencies. Radiographs showed improvement in spinal osteoporosis and cortical bone dimensions and arrest of progressive acetabular protrusion. Areal bone density increased substantially (lumbar spine z-score from ,2.2 to + 1.8). Tetracycline-labeled bone biopsy specimens were taken before and after 18 months of intensive treatment. The second biopsy showed suppression of bone turnover and a doubling of trabecular thickness, with no mineralization defect, and no osteopetrosis. Conclusions: Intensive bisphosphonate treatment prevented the development of deformity and disability and improved hearing in this child with IH. The dose of bisphosphonate, which is substantially greater than is usually used in pediatric bone disease, had no adverse effects, in particular on bone mineralization. [source] Increased risk of citrate reactions in patients with multiple myeloma during peripheral blood stem cell leukapheresisJOURNAL OF CLINICAL APHERESIS, Issue 4 2010Jill Adamski Abstract The citrate based anticoagulant ACD is commonly used in apheresis procedures. Due to its ability to decrease ionized calcium, citrate may cause unpleasant symptoms, such as paresthesias and muscle cramps, in patients undergoing therapeutic and donor apheresis. We noticed that patients with multiple myeloma (MM) undergoing autologous stem cell leukapheresis appeared to have more citrate reactions when compared to other patients undergoing the same procedure. A retrospective chart review was performed to evaluate 139 (of 151) consecutive patients with MM, amyloidosis, hematological and solid malignancies who had autologous peripheral blood stem cell collection between January 2007 and February 2008. Citrate reactions, ranging from mild (e.g., perioral tingling and parasthesias) to severe (e.g., nausea/vomiting and muscle cramps) were noted for 35 patients. Twenty-three of 63 patients with MM had documented citrate reactions, which was significantly higher than those with other hematological and solid malignancies (37% vs. 20%; P < 0.05, Relative Risk (RR) = 1.9). The severities of citrate reactions were the same in both groups; approximately 50% of patients in each group received i.v. calcium gluconate for treatment of hypocalcemia. No correlation between bisphosphonate therapy and citrate reactions were noted in our study group. Examination of available laboratory values related to calcium homeostasis, liver, and renal function failed to reveal a mechanism for the increase in citrate reactions observed. In summary, this single institution retrospective study indicates that patients with MM are more sensitive to citrate-induced hypocalcemia during leukapheresis when compared to patients with other hematological and solid malignancies. Strategies for decreasing citrate reactions (e.g., supplemental calcium and slowing return rates) should be considered for patient safety and comfort, especially in the MM population, on a prophylactic rather than reactive basis. J. Clin. Apheresis 25:188,194, 2010. © 2010 Wiley-Liss, Inc. [source] The effects of RANKL inhibition on fracture healing and bone strength in a mouse model of osteogenesis imperfectaJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 2 2008Demetris Delos Abstract Currently, the standard treatment for osteogenesis imperfecta (OI) is bisphosphonate therapy. Recent studies, however, have shown delayed healing of osteotomies in a subset of OI patients treated with such agents. The current study sought to determine the effects of another therapy, RANKL inhibition, on bone healing and bone strength in the growing oim/oim mouse, a model of moderate to severe OI. Mice [73 oim/oim and 69 wild-type (WT)] were injected twice weekly with either soluble murine RANK (RANK-Fc) (1.5 mg/kg) or saline beginning at 6 weeks of age. At 8 weeks of age, the animals underwent transverse mid-diaphyseal osteotomies of the right femur. Therapy was continued until sacrifice at 2, 3, 4, or 6 weeks postfracture. At 6 weeks post-fracture, greater callus area (6.59,±,3.78 mm2 vs. 2.67,±,2.05 mm2, p,=,0.003) and increased radiographic intensity (mineral density) (0.48,±,0.14 vs. 0.30,±,0.80, p,=,0.005) were found in the RANK-Fc versus saline oim/oim group, indicating a delay in callus remodeling. Despite this delay, mechanical tests at 6 weeks postfracture revealed no significant differences in whole bone properties of stiffness and failure moment. Further, RANKL inhibition resulted in a greater failure moment and greater work to failure for the nonfractured contralateral WT bones compared to the nonfractured saline WT bones. Together, these results demonstrate that RANKL inhibition does not adversely affect the mechanical properties of healing bone in the oim/oim mice, and is associated with increased strength in intact bone in the WT mice. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:153,164, 2008 [source] Attempted randomized controlled trial of pamidronate versus calcium and calcitriol supplements for management of steroid-induced osteoporosis in children and adolescentsJOURNAL OF PAEDIATRICS AND CHILD HEALTH, Issue 11 2005JJ Brown Objectives: To describe an attempted interventional trial for glucocorticoid-induced osteoporosis in children and adolescents and to discuss the reasons for trial failure to inform future interventional studies in this important group of patients. Methods: Prospective randomized controlled trial comparing the effect of bisphosphonate therapy with calcium and vitamin D supplementation on bone mineral accrual is described. For non-trial patients, retrospective analysis of the effect of calcium and vitamin D supplementation combined with bisphosphonate treatment on bone mineral accrual. Results: Only 12 patients were enrolled in the trial over 4 years. Bisphosphonate recipients (n = 5) had a mean annual percentage increase in lumbar spine bone mineral density of 8.76 ± 5.2% compared to 6.6 ± 4.0% in the calcium/vitamin-treated group (difference not significant). Mean annual change in lumbar spine areal bone mineral density in non-trial patients (n = 11) was 3.72 ± 2.5%. Conclusion: Conducting a randomized controlled trial in this group of corticosteroid users is difficult, given the unpredictable nature of the underlying disease and intermittent need for steroid treatment. The trial failed through inadequate recruitment combined with discontinued interventions. [source] Risk of upper gastrointestinal bleeding with oral bisphosphonates and non steroidal anti-inflammatory drugs: a case-control studyALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 11 2009M. ETMINAN Summary Background, Gastrointestinal injuries including gastric ulcers have been reported with oral bisphosphonate therapy. However, the risk of the more serious upper gastrointestinal bleeding (UGB) especially in the community setting with these drugs remains unknown. Similarly, the risk of UGB among users of both bisphosphonates and non steroidal anti-inflammatory drugs (NSAIDs) in the community is also unknown. Aim, To explore the risk of more serious UGB among users of bisphosphonates and the risk of UGB among users of both bisphosphonates and NSAIDs in the community. Methods, We conducted a case-control study within a cohort of Quebec residents who had received a revascularization procedure from 1995 to 2004. Cohort members were followed up from the date of their first procedure until the earliest of: (1) study outcome, (2) date of death or (3) end of health care coverage. Cases were defined as those with the first diagnosis of a UGB. For each case, 20 controls were selected and matched to the cases by index date, age and cohort entry. Adjusted odds ratios for current use of bisphosphonates, NSAIDs and co-therapy of both drugs were computed. Results, Within the initial cohort, 3253 incident cases of UGBs and corresponding 65 060 matched controls were identified. The adjusted odds ratio (OR) for UGB by current users of bisphosphonates was 1.01 (95% CI, 0.72,1.43). Current NSAID use was associated with an increased risk of UGB OR = 1.75; 95% CI, 1.53,1.99. The OR for use of bisphosphonates and NSAIDs was elevated OR = 2.00; 95% CI, 1.12,3.57. This risk was still elevated for users of bisphosphonates and COX-2 inhibitors [OR = 2.38 (95% CI, 1.26,4.50)]. Conclusion, We found no evidence of an increase in the risk of UGB among current users of bisphosphonates. The risk of combined NSAID and bisphosphonate therapy was increased, but this risk was not higher than the risk for NSAID users alone. [source] Osteonecrosis of the Mandible or Maxilla Associated with the use of New Generation BisphosphonatesTHE LARYNGOSCOPE, Issue 1 2006Matthew C. Farrugia DO Objective: The use of bisphosphonates is well established for the treatment of patients with metastatic bone disease, osteoporosis, and Paget's disease. Osteonecrosis of the mandible or maxilla associated with the use of bisphosphonates is a newly described entity never before discussed in the otolaryngology literature. In this paper, we review a series of patients diagnosed with osteonecrosis, all treated with new generation bisphosphonates. Our objective is to inform and educate others, particularly otolaryngologists/head and neck surgeons, about this drug induced entity, a condition that should be recognized early to avoid potential devastating consequences. Study Design: Retrospective chart review of a series of patients from a tertiary referral center. Methods: Pathology reports of specimens submitted from either the mandible or maxilla were reviewed from the previous 12 months. Any patient diagnosed with osteonecrosis without evidence of metastatic disease at that site was included; those with a previous history of radiation therapy were excluded. Each patient's medical history and profile were reviewed. Results: Twenty-three patients were identified with osteonecrosis of the mandible or maxilla. All of these were associated with the use of new generation bisphosphonates: zolendronate (Zometa, Novartis), pamidronate (Aredia, Novartis), and alendronate (Fosamax, Merck). Eighteen patients with known bone metastases had been treated with the intravenous form, whereas five patients with either osteoporosis or Paget's disease were using oral therapy. Patients typically presented with a nonhealing lesion, often times the result of previous dental intervention. Although the majority of these patients were treated with conservative surgical debridement, we present a case requiring a near total maxillectomy. Conclusions: Drug induced osteonecrosis of the mandible or maxilla has been recently recognized as a sequelae of treatment with the new generation of bisphosphonates. Most patients can be treated with conservative surgical debridement and cessation of bisphosphonate therapy, whereas a few may require radical surgical intervention. Other recommendations include regimented prophylactic care with an assessment of dental status before the administration of bisphosphonates, avoidance of dental procedures, and close monitoring of oral hygiene. [source] The oral health status of patients on oral bisphosphonates for osteoporosisAUSTRALIAN DENTAL JOURNAL, Issue 4 2008R Kunchur Abstract Background:, The oral health status of patients on bisphosphonates is the key to the patient's ongoing health and well-being. If they are orally healthy, invasive bone procedures, particularly extractions can be avoided, then the risk of osteonecrosis of the jaws (ONJ) is low. Methods:, The records of 49 consecutive patients on oral bisphosphonates, referred to the Oral and Maxillofacial Surgery Unit (OMSU) for an oral health check and probable extractions, were retrospectively reviewed. The DMFT, periodontal and pathologic state were calculated from the OPG radiographs. An age and gender matched control group, from patients referred to the OMSU but who were not on oral bisphosphonates, were similarly assessed. Community data were also obtained. Results:, The DMFT score for the oral bisphosphonate group was 29: Decayed 3, Missing 10, Filled 16. The control group DMFT score was 24: Decayed 5, Missing 11, Filled 8. Both groups had advanced periodontal disease (over 95 per cent) and were medically compromised (over 90 per cent). The DMFT for general community data for age matched government pensioners was 19.1: Decayed 0.8, Missing 10.4, Filled 7.9. With severe periodontal disease 23 per cent. Thus, the oral health of the oral bisphosphonate group was similar to the control group and both had more decayed teeth and periodontal disease than community values. Conclusions:, This study confirms that one cannot assume that a patient on an oral bisphosphonate for osteoporosis has a healthy mouth. It supports the view that all patients on bisphosphonates need to be seen by a dentist either before or soon after commencement of bisphosphonate therapy. [source] Bisphosphonate therapy for patients with breast carcinomaCANCER, Issue S3 2003Who to treat, when to stop Abstract Bisphosphonates have become well established in the treatment of patients with metastatic bone disease, although the optimal use of these agents has not been defined clearly. Randomized, controlled trials have demonstrated that treatment with intravenous pamidronate can significantly reduce the rate of skeletal-related events in patients with bone metastases from myeloma or advanced breast carcinoma. To date, there are few data from controlled, randomized studies to support the use of bisphosphonates in patients with bone metastases from malignancies other than breast carcinoma and myeloma. The optimal duration of treatment is unknown. Recent data have demonstrated that prolonged treatment is tolerated well, with no obvious toxicity. Generally, treatment is continued irrespective of the development of skeletal-related events and until there is a substantial decline in performance status. The widespread use of bisphosphonates will have major financial implications. Retrospective studies have suggested that the cost-effectiveness ratio is high for patients with advanced breast carcinoma. These ratios may be improved by targeting therapy to patients at high risk of developing complications from skeletal metastatic disease. Among patients with skeletal metastases from breast carcinoma, a recent retrospective analysis demonstrated that patients with disease confined to the skeleton were at greater risk of pathologic fractures compared with patients who had additional extraosseous disease. It is interesting to note that approximately two-thirds of patients with advanced breast carcinoma in the randomized trials of intravenous pamidronate had disease confined to the skeleton. The use of markers of bone turnover to identify patients who are most likely to benefit from bisphosphonate therapy or to identify patients who will respond to such therapy is the subject of further investigation. There are conflicting data on the use of bisphosphonates as an adjuvant therapy. Currently, such treatment should occur only as part of a clinical trial. Bisphosphonates can be used to prevent bone loss as a result of therapy for malignant disease, e.g., premature menopause in patients with early breast carcinoma. Cancer 2003;97(3 Suppl):854,8. © 2003 American Cancer Society. DOI 10.1002/cncr.11146 [source] Effectiveness and cost of bisphosphonate therapy in tumor bone diseaseCANCER, Issue S3 2003Jean-Jacques Body M.D., Ph.D. Abstract BACKGROUND Tumor-induced osteolysis due to breast carcinoma and myeloma is responsible for a considerable morbidity that severely impairs patients'quality of life. Osteoclast-mediated bone resorption is reported to be increased markedly in patients with tumor bone disease and can be inhibited by bisphosphonate therapy. METHODS The incidence of skeletal complications and the effectiveness of bisphosphonate therapy in patients with breast carcinoma metastatic to bone or in those with myeloma were derived from large-scale, long-term, placebo-controlled trials with clodronate or pamidronate. To the authors' knowledge, there are few studies published to date evaluating the cost-effectiveness of bisphosphonate therapy, and the majority that do exist often are based on models and are applicable only to a particular health care system. RESULTS From the placebo groups of the above-mentioned trials, one can estimate that approximately 25,40% of the patients with breast carcinoma metastatic to bone will require radiotherapy for bone pain and approximately 17,50% will sustain incident vertebral fractures yearly. The incidence of complications is reported to be lower in myeloma patients. The prolonged administration of bisphosphonates reportedly can reduce the frequency of skeletal-related events by approximately 25,50%. Maximal efficacy appears to have been achieved with the current therapeutic schemes based on monthly intravenous infusions. Beneficial effects appear to be obtained more readily using the intravenous route rather than the oral route. The costs of bisphosphonate therapy appear to be higher than the cost savings from the prevention of skeletal-related events. The costs per quality of life-adjusted year have been estimated to be > $100,000, but more research is needed. Limited data suggest that zoledronic acid will not reduce treatment costs but the short infusion time will lead to substantial time savings for patients and for outpatient oncology facilities. CONCLUSIONS As is the case for many agents used in oncology, bisphosphonates remain a relatively expensive therapy. More studies are needed to evaluate their cost-effectiveness ratio correctly. A ceiling effect has been reached with current therapeutic schemes and tailoring therapy to the individual patient needs to be evaluated correctly to increase therapeutic effectiveness and improve quality of life further without increasing treatment costs. Cancer 2003;97(3 Suppl):859,65. © 2003 American Cancer Society. DOI 10.1002/cncr.11139 [source] Decreased bone density and treatment in patients with autosomal recessive cutis laxaACTA PAEDIATRICA, Issue 3 2009C Noordam Abstract Aim: Due to the occasional association pathological fractures and osteoporosis we evaluated four patients with cutis laxa syndrome for skeletal anomalies. Patient/Methods: We prospectively evaluated four patients, a male and a female child and a brother-sister sib pair, with dysmorphic features, growth delay, joint anomalies, psychomotor retardation and congenital cutis laxa. The clinical features and the family history were suggestive for autosomal recessive cutis laxa syndrome type II, partially overlapping with geroderma ostedysplastica. Skeletal survey, sequential bone density measurements, endocrine and metabolic investigations were performed including N- and O-linked glycosylation analysis. ATP6V0A2 and FBLN5 mutations were ruled out in all patients. Results: All children were diagnosed with significantly decreased bone density, especially in the lumbar spine, including spontaneous vertebral and rib fractures in three children. Following 24 months of bisphosphonate treatment a total restitution of bone density was observed in three cases and no relapse was detected in the 2-year follow-up period. A spontaneous improvement was found in one female during puberty. Conclusion: Bone disease might occur early in the course in autosomal recessive cutis laxa syndrome. We report on a significant clinical improvement and stabilization in our patients following bisphosphonate therapy. We suggest early, systemic evaluation and follow up of bone density in all children presenting with inherited cutis laxa. [source] The use of molecular markers of bone turnover in the management of patients with metastatic bone diseaseCLINICAL ENDOCRINOLOGY, Issue 6 2008Markus J. Seibel Summary Biochemical markers of bone turnover are widely used in clinical practice. These indices have been shown to be associated with the occurrence, prognosis and therapeutic response of malignant bone lesions. For example, markers of bone resorption are often elevated in patients with established bone metastases and while this may point to a role of these markers in the diagnostic workup of cancer patients, the available evidence does not permit any final conclusions as to the accuracy and validity of the presently used markers in the early diagnosis of bone metastases. Many bone turnover markers appear to respond to antiresorptive and antineoplastic therapies, and recent evidence from prospective trials suggests that the aim of bisphosphonate therapy should be to normalize rates of bone remodelling to optimize therapeutic and prognostic outcomes. However, it remains unknown whether the use of bone markers in the routine clinical setting has any defined beneficial effects on overall outcome in cancer patients. Clearly, bone turnover markers have insufficient diagnostic or prognostic value to be used in isolation; however, the combination of these markers with other diagnostic techniques may improve clinical assessment of patients with bone-seeking cancers. This article reviews the available evidence (as of August 2007) on the clinical use of bone turnover markers in the management of patients with metastatic bone disease. [source] Implant Placement in Patients with Oral Bisphosphonate Therapy: A Case SeriesCLINICAL IMPLANT DENTISTRY AND RELATED RESEARCH, Issue 3 2010Ghasem Omati Shabestari DDS ABSTRACT Background: Although the effect of bisphosphonates on dental implant osseointegration is not clear, dental implant failures attributable to oral bisphosphonate therapy have been reported in patients with osteoporosis. Purpose: The aim of this study was to evaluate implant survival in patients with a history of bisphosphonate therapy in a retrospective survey. Materials and Methods: A total of 46 ITI implants placed in 21 osteoporotic patients (females; average age 53 years, range 42,79 years) were evaluated with regard to probing depth, mobility, thread exposure, and bleeding on probing. All patients were under oral bisphosphonate therapy. Results: None of implants showed mobility and all patients could be considered free from peri-implantitis. Time of bisphosphonate therapy before and after implant insertion showed no statistically significant influence on PD, BOP, and TE. Likewise, implant location, prosthetic type, and opposing dentition had no statistically significant influence on the clinical and radiological parameters of implants. Conclusion: Within the limitations of this study, it could be concluded that neither being on oral bisphosphonate treatment before implant placement nor starting bisphosphonate therapy after implant installation might jeopardize the successful osseointegration and clinical and radiographic condition of the implants. [source] | ||||||||||