Biphosphonate Therapy Research Articles

Adherence to weekly oral bisphosphonate therapy: cost of wasted drugs and fractures

In an observational cohort of patients treated with biphosphonates (BP), we observed that poor adherence to these drugs causes important expenditures in terms of avoidable fractures. Of particular interest are the amounts of money wasted by patients who did not take their BPs long enough to obtain a clinical benefit. A large proportion of patients initiated with oral weekly BP therapy stop their treatment within the first year. The objective of this study was to estimate the impact of the poor adherence to BPs in terms of drug wasted and avoidable fractures. The study was done on primary and secondary prevention cohorts from the Régie de l'assurance maladie du Québec (Québec). The concept of the "point of visual divergence" was used to determine the amount of wasted drug. The risk of fracture was estimated using Cox regression models. The hazard ratios of compliant patients (+80%) versus non compliant patients were used to estimate the number of fractures saved. The cost of wasted drugs was $25.87 per patient initiated in the primary prevention cohort and $30.52 in the secondary prevention cohort. If all patients had been compliant, 110 fractures would have been avoided in the primary prevention cohort and 19 fractures in the secondary prevention cohort. The cost of these avoidable fractures per patient initiated on BP therapy was $62.95 in primary prevention cohort and $330.84 in secondary prevention cohort. This study confirms that poor adherence to oral BPs leads to a significant waste of money and avoidable fractures.

Predictors of Osteopenia/Osteoporosis in Children with Acute Lymphoblastic Leukemia.

Background: Loss of bone mineral is a major problem in children with acute lymphoblastic leukemia (ALL), resulting in acute and chronic morbidity. About 30–40% of children with ALL will develop osteopenia/osteoporosis (OP) and about 10–15% will suffer from fractures. Identifying a population at high risk for OP is important to implementing a preventive strategy (e.g. biphosphonate therapy). So far predictors of OP in association with ALL in children are uncertain. Hence we undertook the following study to evaluate predictors of OP in children with ALL treated according to Dana-Farber Cancer Institute protocols.Aim: To evaluate the relationship between lumbar spine bone mineral density (LS-BMD) Z scores in patients with ALL during maintenance therapy and the variables of age at diagnosis (< 10 vs. ≥ 10-years), risk group [Standard (SR) vs. high-risk (HR)], gender (male vs. female) and LS-BMD at diagnosis.Methods: Children (≤ 18-years) diagnosed with ALL during the period 1995–2006 who were in first clinical remission, were included in the study. LS-BMD was measured using dual-energy X-ray absorptiometry (DEXA) at the time of diagnosis (n=88) and during the maintenance phase of therapy (n=119). The actual values of LS-BMD were expressed as age and gender matched Z-scores based on local population norms. Regression analyses were used to evaluate the risk of osteopenia, defined as LS-BMD Z score < -1.00, and osteoporosis, defined as LS-BMD Z score < -2.00. We evaluated the effect of age at diagnosis, gender, ALL risk category and LS-BMD at diagnosis on the LS-BMD during maintenance phase of therapy.Results: Of the 119 patients, 19 (16%) were ≥ 10-years of age, 46 (39%) were girls and 41 (34.5%) had HR ALL. At diagnosis 29 of 88 (33%) patients had osteopenia and 6 (6.8%) had osteoporosis whereas, during maintenance therapy, 47/119 patients (39.5%) had osteopenia and 10 (8.4%) patients had osteoporosis. LS-BMD at diagnosis had a positive linear relationship with LS-BMD during maintenance therapy (Pearson correlation coefficient 0.721, p<0.001). Older children and children with HR ALL had a significantly higher risk of osteopenia compared to younger children (p=0.01) and children with SR ALL (p=0.019). Age and risk category were confounding variables since all children ≥ 10 years were classified as HR ALL. Gender by itself had no significant effect. However, the effect of age on the LS-BMD during maintenance phase was gender-dependent with older girls having lower LS-BMD compared to older boys.Conclusions: Osteopenia and osteoporosis (OP) are common in children with ALL. Age over 10-years, female gender, HR ALL and lower LS-BMD at diagnosis are predictors of lower LS-BMD during the maintenance phase of therapy. Using these variables it is feasible to develop a predictive model to define the risk of OP during the maintenance phase of therapy. Larger prospective studies will better define this risk.

Osteonecrosis of the Jaw in Multiple Myeloma Patients (the IFM Registry).

PURPOSE: to describe the incidence, characteristics and risk factors for osteonecrosis of the jaw (ONJ) in multiple myeloma (MM).PATIENTS AND METHODS : retrospective review of 51 ONJ collected from the IFM centers. For MM, age at diagnosis, isotype, DS staging, nature of chemotherapy and number of Stem-Cell Transplantation were the same that expected.RESULTS: ONJ occurred predominantly in the mandible (70%). The median time of exposure to biphosphonates (BP) was 45 months (4 to 144 months). BP therapy included: zoledronate (85%), pamidronate (10%), clodronate (5%), all of the patients have received intravenous BP before, two patients have no BP at the time of diagnosis of ONJ.RISK FACTORS: dental extraction (59%) other dental care (5%), dental infection (24%), others (30%), no risk factor (10%). SYMPTOMS: pain (92%), purulent discharge (37%), presence of exposed bone (60%), fracture (2%).MANAGEMENT: BP discontinuation (84%), medical treatment (86%), removal of sequestra (51%), extensive surgery (20%).EVOLUTION: improvement (55%), chronical symptoms (70%).INCIDENCE: we have not the number of exposed patients but: 46 centers/73 reported no ONJ.The first report was march 2001. In the same period, 1695 patients where included in IFM trials and only 16 ONJ where observed. Year of diagnosis: before 2004: 5 cases; 2004: 11 cases; 2005:26 cases; 2006: 7 cases; 2007(6 months): 2cases.CONCLUSION: ONJ is an adverse side effect of amino BP therapy (zoledronate>pamidronate), is time dependant and often after dental extraction. Preventive recommandations applied in 2005 can explain the decreasing incidence of ONJ in our study.

PD6-3-3: Medical and economical impact of bone metastases in lung cancer patients: a prospective French national, multicentric study (GFPC 06-01 study)

Bone metastases are an important emerging problem in patients with lung cancer and are leading to increasing consumption of health care resources. To assess the epidemiology, the management strategies and the costs of bone metastases in lung cancer; to model the management of these patients by a Markov model in order to evaluate the effectiveness of different therapeutic strategies. prospective, national, multicentric, observational, epidemiological study planned to include 500 patients between may 2006 and may 2007, with a one year follow up, a monthly report of skeletal-related events and resources consumptions. The economic analysis is limited to the direct costs with the health care payer’s perspective. At this time, 404 patients are included by 36 centres: men: 77,2%, median age: 61 (39-84) years, non small cell lung cancer: 90%. Bone diagnosis metastases is made by scintigraphy (59.7%), standard radiology or RMI (3.4%), and bone-scan (36.9%). At inclusion the median number of lesions was 4; 74.4% of patients receive an analgesic treatment, 41.5% a biphosphonates therapy (zoledronate in 83% of cases), 20.5% a radiotherapy and 5%.had a bone-surgery. complete demographic, clinical and economical datas will be presented at the IASCL meeting.

Paget's Cervical Disease with Spinal Cord Compression and Atlantoaxial Instability: Case Report

Authors report about the case of a 65-year-old woman presenting with a polyostotic Paget's disease, with axis, lumbar, and calcaneum involvement. The C2 vertebral lesion was responsible for spinal cervical cord compression and atlantoaxial instability because of a pathological odontoid peg fracture. The patient was operated on by a posterior approach allowing spinal cord decompression, pathological tissue sampling, and C0-C4 stabilization. Pathological examination confirmed the radiological diagnosis of Paget's disease and the biphosphonate therapy was started. Radiological follow-up showed a good craniocervical stability and an unchanged axis lesion. Even if treatment of pagetic spinal stenosis symptoms should start with medical therapy, surgery can sometimes be preferred to treat neural compression due to spinal instability.

The Use of i. v. Bisphosphonate in Pregnancy-Associated Osteoporosis - Case Study

Diagnosis of pregnancy-associated osteoporosis is often delayed and therapeutic interventions insufficient. A 28-year-old patient (BMI=18.6) with no additional risks for osteoporosis experienced acute lumbosacral pain two months postpartum, while lactating. After conservative therapy, thoracic and lumbar spine were X-rayed: severe pregnancy-associated osteoporosis with vertebral fractures was diagnosed. 2-year treatment with i. v. bisphosphonate ibandronate was initiated (2 mg every 3 months) and calcium and vitamin D supplementation. Rapid improvement was observed. Conclusion: In cases with multiple fractures i. v. bisphosphonate leads to substantial decrease of symptoms and further fractures and significant increase of bone mass density (BMD). In severe cases of pregnancy-associated osteoporosis with multiple fractures i. v. biphosphonate therapy leads to a decrease of symptoms and fracture risk and an increase of bone mass density (BMD).

Paget's Cervical Disease with Spinal Cord Compression and Atlantoaxial Instability: Case Report

Authors report about the case of a 65-year-old woman presenting with a polyostotic Paget's disease, with axis, lumbar, and calcaneum involvement. The C2 vertebral lesion was responsible for spinal cervical cord compression and atlantoaxial instability because of a pathological odontoid peg fracture. The patient was operated on by a posterior approach allowing spinal cord decompression, pathological tissue sampling, and C0-C4 stabilization. Pathological examination confirmed the radiological diagnosis of Paget's disease and the biphosphonate therapy was started. Radiological follow-up showed a good craniocervical stability and an unchanged axis lesion. Even if treatment of pagetic spinal stenosis symptoms should start with medical therapy, surgery can sometimes be preferred to treat neural compression due to spinal instability.

Osteonecrosis of the Jaw (ONJ) in Patients with Multiple Myeloma, Receiving Bisphosphonate Therapy, Is Independent of Renal Function: Single Institute Experience of an Emerging Clinical Problem.

Introduction: Use of bisphosphonate (zoledronic acid and pamidronate) for prevention of pathological fractures is standard of care in multiple myeloma (MM) patients with osteolytic bone lesions. While clinical trials have investigated effectiveness of these agents for up to 2 years of use, clinical practice has incorporated their use indefinitely. With improvement in survival through availability of novel agents in MM patients, the use of bisphosphonate therapy has also prolonged. Recent reports unveiled a new side effect of Bisphosphonate therapy i.e., ONJ, characterized by necrosis of the jawbone with antecedent subluxation or loss of the teeth and ulceration of the gum mucosa. The underlying etiology remains elusive, and in the absence of effective remedy ONJ has raised significant concerns upon the duration of treatment with Bisphosphonate. We investigated the magnitude of this problem among MM patients receiving Biphosphonate therapy at our institute.Methods: We conducted a retrospective review of all patients diagnosed with MM at our institute since 2001 who received bisphosphonate treatment and developed ONJ. Clinical characteristics, prior treatments and renal function prior to development of ONJ were evaluated.Results: Records of 20 pts who developed ONJ were reviewed.The median age of these pts was 57 (range 45–69).Among these, 9 were males, 11 were females. All pts (100%) had stage III MM.11 patients (55%) received 2 or more antimyeloma treatment.14 pts (70%) were on Zoledronic acid, 5 pts (25%) were on Pamidronate, and 1 pt (5%) was first on Zoledronic acid then switched to Pamidronate.Out of those 20 patients, 19 (95%) had normal renal function prior to and after development of ONJ, with Creatinine level range of (0.5–1). Only 1 patient (5%) had decreased renal function prior to development of ONJ, with Creatinine level of 6.6Conclusion: Although the number of patients reported are small, experience at our center with ONJ in MM patients who were on Bisphosphonate failed to show any association with renal function. Interestingly all patients who developed ONJ were stage III MM.There are currently no established guidelines for prevention or treatment of this disorder.

Effect of kidney transplantation on bone

A broad range of different factors aggravates renal osteodystrophy, which is present in virtually all patients with chronic kidney disease and after successful kidney transplantation. Altered hormonal status, including sex hormones and parathyroid hormone (PTH), a deficit of 1,25(OH)(2) vitamin D(3) (calcitriol), immunosuppressive therapy and post-operative immobilization contribute to a progressive loss of bone density and structure. The decrease of bone mass is particularly prominent during the first 6 months after kidney transplantation and is associated with an increased number of fractures, both compared with the normal population as well as with dialysis patients. At particular risk are patients with a history of diabetes, long duration of haemodialysis and post-menopausal women. To prevent post-transplant bone loss prescription of steroids should be minimized and withdrawn as early as possible. Additional intake of alpha-calcidol [25(OH) vitamin D(3)] or calcitriol, despite normal serum levels, reduces persistent hyperparathyroidism after kidney transplantation, improves intestinal calcium absorption and activates osteoblasts. Inhibition of osteoclasts by biphosphonate therapy seems to effectively reverse bone loss during the early and late course of kidney transplantation. However, as the majority of transplant recipients have a low-turnover bone disease, inhibition of osteoclasts, through which bone turnover is impaired, might further reduce osteoblast activity and promote osteoid synthesis. Most investigations were small-scale studies with 10-100 participants and a follow up of only 12 months. This makes conclusions on the effect of any intervention on the fracture rate impossible. Larger, randomized multicentre studies investigating bone-sparing therapy on hard end points are therefore advocated.

An update: Health economics of managing multiple myeloma

Based on Medline search, a summary is provided of recent health economic evidence in published literature relating to the management of multiple myeloma. The following major components of current multiple myeloma treatments are discussed: induction chemotherapy, high-dose chemotherapy supported by autologous peripheral stem cell transplantation (ASCT), long-term biphosphonates therapy to prevent skeletal events and recent advances for the treatment of relapsed or refractory multiple myeloma and under evaluation in primary treatment (thalidomide and bortezomib). Our study shows that there still appears to be a need for health economic information to confirm the cost-effectiveness of stem cell support versus high-dose chemotherapy without stem cell support, as well as to assess optimal biphosphonate treatment regimens. There is also a clear need for peer reviewed economic evaluations of novel therapies such as thalidomide and Bortezomib in the treatment of multiple myeloma at different stages of the disease.

Osteomyelitis of the Jaw in Multiple Myeloma Patients as a Complication of the Treatment with Biphosphonates.

Biphosphonates (zoledronate, pamidronate and clodronate) are frequently used for bone disease prevention and treatment in patients with multiple myeloma. Monthly biphosphonate therapy improves quality of life and in some reports survival. However, biphosponates are associated with adverse effects such as renal impairment and osteonecrosis of the jaws. We have recently described 3 myeloma patients who developed oseomyelitis of the jaw during chronic biphosphonate therapy. In a national survey we found 11 patients from 6 centers in Israel with osteomyelitis of the jaws probably due to prolonged therapy with intravenous biphosphonates. Nine were female. Median age at the time of diagnosis of myeloma was 67 years (range 59–86). nine patients suffered from IgG myeloma, and 2 had light chain disease. In five patients MGUS was known during 4 to 9 years before development of overt myeloma. All patients had received chemotherapy, and 2 underwent ABMT. Median time from diagnosis of myeloma to diagnosis of osteomyelitis of the jaw was 30 months (range 15–48). In six cases osteomyelitis was provoked by dental procedure. In all cases the diagnosis of osteomyelitis was confirmed by bone biopsy and in 7 colonies of Actinomyces Israeli were demonstrated. In one patient Pseudomonas Aeruginosa was also found. All patients had been treated with biphosphonates before diagnosis of osteomyelitis (13 to 48 months): eight with pamidronate, and 3 with zoledronate. The mean total dose of pamidronate was 3190 mg (range 1690–4680), and zoledronate- 72mg (range 16–96). Therapy for osteomyelitis included prolonged antibacterial treatment, surgical debridment, and hyperbaric oxygenation. Acute, and chronic, osteomyelitis of the jaws secondary to biphosphonate therapy, is frequently encountered among myeloma patients and should be reported separately from another complication of biphosphonates, osteonecrosis of the jaws.

Oral avascular bone necrosis associated with chemotherapy and biphosphonate therapy

Oral avascular bone necrosis is an important adverse effect of chemotherapy and biphosphate therapy. To report our experience in oral avascular bone necrosis in cancer patients assigned to undergo chemotherapy. Fourteen patients presenting oral avascular bone necrosis were selected from the clinical files of five Stomatological Clinics in Brazil. Clinical data as well as treatment and prognosis information were obtained from all 14 patients. Twelve patients (86%) were submitted to biphosphonate therapy. The most important symptom was pain, present in all cases, and the mandible was the most common involved site. Most patients (79%) had their conditions managed by antibiotic therapy and surgical debridation; however complete response was achieved in only three cases (21%). Avascular bone necrosis is a serious oral side-effect of cancer chemotherapy, particularly in patients using biphosphonates, and antibiotic therapy and surgical debridation were not able to promote complete response in most cases.

Quelle est la place des biphosphonates dans le traitement de l'algodystrophie sympathique réflexe ?: Analyse critique de la littérature

Objectives. – To evaluate the efficacy of biphosphonates (BPs) in complex regional pain syndrome I or reflex sympathetic dystrophy and to specify their place in this chronic painful syndrome. Methods. – A literature review of Medline and Embase with use of a combination of 3 key words: biphosphonates therapy, reflex sympathetic dystrophy, complex regional pain syndrome I, controlled study. Each article was classified by 2 independent reviewers according to Aguilar's method into high, middle or low quality. Results. – Three second-generation BPs were tested in the treatment of reflex sympathetic dystrophy: pamidronate, alendronate and clodronate. Many open studies investigated pamidronate, but only 2 were randomised and controlled: a low-quality trial comparing pamidronate with placebo and a middle-quality trial comparing pamidronate with calcitonine. Two high-quality trials were performed, 1 with alendronate and 1 with clodronate. Middle-quality trial and high-quality trials reported positive effects on pain with BPs in recent reflex sympathetic dystrophy (disease duration less than eight months). Side effects (fever, asymptomatic hypocalcemia) were observed frequently but disappeared quickly. Conclusion. – BPs can be used in recent reflex sympathetic dystrophy when calcitonin is inefficient or when calcitonin injections are not well tolerated.

Combined chemotherapy and radiotherapy during conception and first two trimesters of gestation in a woman with metastatic breast cancer

A 33-year-old woman with T4cN3 breast cancer with metastases in the skeleton (M1) received five cycles of 5-fluorouracil, epirubicin, and cyclophosphamide (FEC regimen) before conception and during the first trimester. Salvage radiotherapy (28 Gy) was delivered during the 17th week. Tamoxifen and zolendronic acid were also administered throughout the second and third trimesters. The patient was not aware of her pregnancy until the 28th week. A female phenotypically normal infant was delivered in the 35th week of gestation by cesarean section. The child is functioning normally 12 months after delivery. The literature of anthracycline treatment during conception and the first trimester is reviewed. The effects of tamoxifen and biphosphonate therapy on the fetus during pregnancy are also discussed.

Pharmacoepidemiology and rheumatic diseases: 2001-2002.

Pharmacoepidemiology is the branch of epidemiology that focuses on medications and their outcomes, including both adverse events and intended consequences. Such studies have become more prominent in rheumatology as the number of new medications has grown and prescribing databases have become more available. In the past year, the potential cardiovascular complications associated with selective COX-2 inhibitors have become an important concern. A number of pooled analyses suggest the possibility of an increased risk of acute myocardial infarction, and studies of naproxen have found a possible protective effect. Accumulating evidence supports the contention that early initiation of disease modifying antirheumatid drug therapy improves outcomes of patients with rheumatoid arthritis. Open-label extensions of biologic therapies found continued benefits extending several years with the TNF-alpha antagonists, but concerns have arisen regarding tuberculosis and central nervous system demyelination with these agents. Data continue to be published quantifying the risk of osteoporosis associated with glucocorticoids, and the association between biphosphonate therapy and upper gastrointestinal events appears to be less of a concern that originally described.

Interaction of Bisphosphonates with Calcitonin in Monitoring Medullary Carcinoma of the Thyroid

We report the case history of a patient with long standing recurrent medullary carcinoma of the thyroid. Elevation of the serum marker calcitonin coincided with the introduction of biphosphonate therapy and recurrence of tumour was not established. The interaction of biphosphonates with calcitonin is not previously recorded.

Parathyroid hormone‐related peptide in pancreatic neuroendocrine tumours associated with hypercalcaemia

Hypercalcaemia is a common paraneoplastic syndrome. In the context of pancreatic neuroendocrine tumours, it is occasionally caused by secretion of parathyroid hormone-related peptide (PTH-rP). Two patients are reported in whom persistent hypercalcaemia was traced to a large neuroendocrine pancreatic tumour hypersecreting PTH-rP. Resection of the tumour reduced serum levels of calcium and PTH-rP transiently in each case until the patient developed bulky metastatic disease. A 33-year-old woman remained hypercalcaemic after the removal of all four hyperplastic parathyroid glands had rendered circulating parathormone levels undetectable. Radical distal pancreatectomy was followed over the next 4 years by operative debulking of liver metastases, multiple hepatic artery embolisations, octreotide injections and repeated admissions for intravenous fluid and biphosphonate therapy. A 41-year-old man presented with hypercalcaemia as well as features of somatostatinoma syndrome. Symptomatic improvement after radical distal pancreatectomy was short-lived, and hepatic artery embolisation failed to control his rapidly progressive disease. Malignant hypercalcaemia associated with a neuroendocrine pancreatic tumour hypersecreting PTH-rP is difficult to treat and can be life-threatening. Aggressive surgical treatment is recommended initially, while somatostatin analogues and hepatic artery embolisation are alternative therapeutic options for metastatic disease.

Ibandronate treatment in Paget’s disease of bone

Paget’s disease is characterized by an excessive enhancement of bone turnover due to increased osteoclastic bone resorption. Antiresorptive drugs, like calcitonins or bisphosphonates, are therefore used in the treatment of Paget’s disease. At present, bisphosphonates are considered the treatment of choice. The usefulness of bisphosphonates like etidronate or tiludronate is limited to less severe cases, due to their comparatively low antiresorptive potency. More potent bisphosphonates like pamidronate or alendronate are frequently associated with gastrointestinal side effects, when given orally, another problem is poor and variable gastrointestinal resorption. Therefore, intravenous application of bisphosphonates has several advantages. With clodronate and pamidronate, however, the application has to be via intravenous infusion to avoid the risk of renal damage. Ibandronate is a new aminobisphosphonate with a 50-fold higher biological activity than pamidronate in vitro. Two milligrams can be administered safely as an intravenous injection, thus providing a new mode of application for intravenous biphosphonate therapy. We report here our experiences with intravenous ibandronate in Paget’s disease of bone. We compared the efficacy and tolerability of intravenous injection vs. infusion of 2 mg ibandronate, investigated the efficacy of a repeat treatment after relapse of disease activity, and assessed the effects of a dose escalation to 4 and 6 mg ibandronate.

Treatment of tumour-induced hypercalcaemia with the bisphosphonate pamidronate: Dose-response relationship and influence of tumour type

Patients with humoral hypercalcaemia of malignancy appear to respond less well to biphosphonate therapy than hypercalcaemic patients with osteolytic metastases. On the other hand, pamidronate is currently the most potent of the commercially available biphosphonates and it is recommended that its dose be increased as a function of pretreatment calcium levels. We reviewed our experience with pamidronate in 160 patients with tumour-induced hypercalcemia (TIH) persisting after rehydration, particularly the influence of the dose administered, the tumour type and the presence of bone metastatic involvement on the calcaemic and calciuric response to pamidronate therapy. Serum Ca was normalized in 92% of the cases (87% when Ca was corrected for protein levels). After therapy, 59% of the patients developed asymptomatic hypocalcaemia (30% for Corr. Ca levels). A multiparameter regression analysis revealed that the response to pamidronate was significantly (P < 0.01) influenced by initial Ca levels up to days 5-7 and, thereafter, only by the dose received. To confirm the dose effect, we divided the patients into three groups according to the median dose received, namely 0.5 mg/kg (n = 35), 1.0 mg/kg (n = 52), and 1.5 mg/kg (n = 73). The differences among the three groups became significant (P < 0.05) from days 5-7 until the end of the evaluation (days 22-26). Similarly, the success rate, considering Corr. Ca levels, was 80% for the 0.5 and 1.0 mg/kg groups combined, compared to 94% for the 1.5 mg/kg group (P < 0.05). The duration of normocalcaemia was similarly more prolonged in the high-dose group. There was a dose-response relationship only in patients with Ca levels above 3.0 mmol/L and in patients with an elevated index of tubular calcium reabsorption. By contrast, the decrease in Ca levels and in fasting urinary calcium excretion, a sensitive index of bone resorption, were not significantly influenced by the primary tumour site or by the presence of bone metastatic involvement. Our data demonstrate a dose-response relationship for pamidronate in TIH over an efficient hypocalcaemic dose range, at least in patients with an elevated tubular calcium reabsorption, which helps to resolve conflicting data in the literature. We suggest that a dose of around 1.5 mg of pamidronate/kg is optimal for the treatment of TIH, except in patients with mild hypercalcaemia, for whom a dose of 1 mg/kg appears to be sufficient. At these dose levels, the efficacy of pamidronate is not significantly influenced by the tumour type or the degree of metastatic bone involvement.

Increased local bone turnover in hypertrophic osteoarthropathy — Beneficial effect of biphosphonate (pamidronate) therapy

Increased local bone turnover in hypertrophic osteoarthropathy — Beneficial effect of biphosphonate (pamidronate) therapy