Single Infusion Of Zoledronic Acid Research Articles

A single infusion of Zoledronic acid suppressed bone turnover markers for up to seven years: Results from the Zoledronate in the Prevention of Paget's disease (ZiPP) study

A single infusion of Zoledronic acid suppressed bone turnover markers for up to seven years: Results from the Zoledronate in the Prevention of Paget's disease (ZiPP) study

PSAT196 Monostotic Paget's disease of the bone involving the calcaneus

Abstract Introduction Paget's disease of bone (PDB) is a chronic bone disorder that is fairly common in older age. It is characterized by an initial increase in osteoclastic activity followed by excessive osteoblastic activity with disorganized bone architecture. PDB may involve any bone and may be monostotic or polyostotic. Herein, we report the rare occurrence of monostotic Paget's involving the calcaneus. Case Description A 71-year-old white male with PMH of prostate cancer status post radical prostatectomy presented with acute onset severe left heel and ankle pain. Pain was localized to the retrocalcaneal area and heel pad limiting his physical activity. He denied recent trauma. Physical exam was significant for swelling and tenderness of the left heel. Left foot X-rays showed a slightly enlarged calcaneus with very coarse trabeculae consistent with PDB. A total body bone scan done previously because of the prostate cancer showed intense uptake in the left calcaneus but no significant uptake elsewhere. Laboratory workup showed an elevated total serum alkaline phosphatase of 164 U/L (40-129 U/L) and bone specific alkaline phosphatase 65 ug/L (0.0-20 ug/L). He was treated with a single infusion of Zoledronic acid with good clinical response evidenced by improvement in pain and swelling as well as a significant decrease in bone specific alkaline phosphatase to 10 ug/L six months post-infusion. Discussion Monostotic PDB only represents about 20% of PDB cases. The pelvis is the most common location followed by the femur as described by Bachiller-Corral et al (Bone, 2013). In our review of the English literature, we found only nine cases of monostotic PDB involving the calcaneus. The mean age of presentation was 60 years old and most of the cases presented as chronic heel pain not responding to conservative pain alleviating measures. Conventional radiography showed the characteristic features of PDB but the changes observed were difficult to differentiate from that of a malignant process. That led to further imaging in most cases by either CT, MRI scan or SPECT scan. Three out of nine patients were reported to receive bisphosphonate therapy with successful remission with a long duration of disease suppression. Good response to therapy highlights the importance of proper diagnosis. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Durability and delayed treatment effects of zoledronic acid on bone loss after spinal cord injury: a randomized, controlled trial.

A single infusion of zoledronic acid (ZOL) after acute spinal cord injury (SCI) attenuates bone loss at the hip (proximal femur) and knee (distal femur and proximal tibia) for at least 6 months. The objective of this study was to examine the effects of timing and frequency of ZOL over 2 years. In this double-blind, placebo-controlled trial, we randomized 60 individuals with acute SCI (<120 days of injury) to receive either ZOL 5-mg infusion (n=30) or placebo (n=30). After 12 months, groups were again randomized to receive ZOL or placebo, resulting in four treatment groups for year 2: (i) ZOL both years; (ii) ZOL year 1, placebo year 2; (iii) placebo year 1, ZOL year 2; and (iv) placebo both years. Our primary outcome was bone loss at 12 months; compared to placebo, a single infusion of ZOL attenuated bone loss at the proximal femur, where median changes relative to baseline were -1.7% to -2.2% for ZOL versus -11.3% to -12.8% for placebo (p < 0.001). Similarly, the distal femur and proximal tibia showed changes of -4.7% to -9.6% for ZOL versus -8.9% to -23.0% for placebo (p ≤ 0.042). After 24 months, differences were significant at the proximal femur only (-3.2% to -6.0% for ZOL vs. -16.8% to -21.8% for placebo; p ≤ 0.018). Although not statistically significant, median bone density losses suggested some benefit from two annual infusions compared to a single baseline infusion, as well as from a single infusion 12 months after baseline compared to 2 years of placebo; therefore, further investigation in the 12-month to 24-month treatment window is warranted. No unanticipated adverse events associated with drug treatment were observed. In summary, ZOL 5-mg infusion after acute SCI was well-tolerated and may provide an effective therapeutic approach to prevent bone loss in the first few years following SCI. © 2021 American Society for Bone and Mineral Research (ASBMR).

SUN-386 Treatment Outcomes of Intravenous Zoledronic Acid vs Oral Alendronate in Postmenopausal Women with Osteoporosis

In real practice, many patients with osteoporosis are poorly compliant with oral bisphosphonate, partly due to gastrointestinal side effects and partly due to medication procedure leading to premature termination of treatment. Once yearly intravenous zoledronic acid is well tolerated; little or no gastrointestinal effects and effective drug in treatment of postmenopausal osteoporosis with favourable dosing regimen to improve compliance of patients. So this study aims to study treatment outcomes of intravenous zoledronic acid vs oral alendronate in postmenopausal women with osteoporosis. This study was a randomized open label comparative study and included 94 postmenopausal women with osteoporosis. In this study, once yearly zoledronic acid (ZOL) infusion provided a greater reduction of serum procollagen type 1 N propeptide (P1NP) at 3 months than once weekly oral alendronate (ALN). Percentages of P1NP change in ZOL group was -70.25±17.51% and ALN group was -60.61±18.87% (P= 0.012). A decrease of P1NP ≥40% was observed in the majority of patients in both groups (89.4% in ZOL group and 85.1% in ALN group) (P= 0.536). ZOL was non-inferior to ALN in terms of BMD change at lumbar spine (4.8±5.5% in ZOL versus 4.9±4.5% in ALN treated patients) with P value of 0.922 and also at total hip (3.8±8.0% in ZOL versus 3.8±7.5% in ALN group) (P= 0.970). Two cases (4.3%) of new fractures was observed in ZOL group whereas 4 cases (8.5%) of new fractures occurred in ALN group over one year of study. The overall frequencies of treatment related adverse effects were similar between ZOL group (57.4%) and ALN group (42.6%) (P= 0.149). ZOL group showed significantly increased frequencies of musculoskeletal pain (57.4%) and acute phase reaction (12.8%) and 12.8% of participants in ALN group complained of heartburn. The overall preference to continue current medication was higher in ZOL group than ALN group (P= 0.002). The participants treated with ZOL were tend to have more satisfaction (P= 0.026) and willing to receive it longer period (P< 0.001).Compared to weekly oral alendronate therapy in treatment of postmenopausal osteoporosis, yearly infusion of 5 mg zoledronic acid infusion produced a significant greater response in serum P1NP at 3 months and similar change in BMD at one year of treatment and overall frequencies of adverse effects were similar between two treatment groups with excellent patient preference and satisfaction after zoledronate treatment. Reference: (1) Al-Bogami et al (2015) Favorable therapeutic response of osteoporotic patients to treatment with intravenous zoledronate compared with oral alendronate. Saudi Med J. 36(11):1305-1311. (2) Saag et al (2007) A single zoledronic acid infusion reduces bone resorption markers more rapidly than weekly oral alendronate in postmenopausal women with low bone mineral density. Bone. 40:1238-1243.

Long term effects on biochemical bone markers of a single infusion of zoledronic acid in Paget disease of bone

BackgroundThe aim of the present study is to evaluate long term biochemical response to a single dose of zoledronic acid in patients with Paget disease of bone, as well as evaluating the value of bone turnover markers in diagnosis and follow-up. MethodsThis is an observational, descriptive and prospective study. Included patients received a single-dose intravenous infusion of 5 mg zoledronic acid. Bone turnover markers were measured at baseline, and in every follow up visit. ResultsThirty-nine patients with a mean follow-up of 56.49 months were included. At the time Paget disease was diagnosed, all of the patients (100%) had high serum procollagen type 1 amino-terminal propeptide values, but not all patients had high serum C-terminal telopeptide and alkaline phosphatase values (85% and 89% respectively). Biochemical response to therapy occurred in 38 out of 39 patients (97%). Two patients had partial response at 6 months but complete response thereafter. Only one patient relapsed (nadir procollagen type 1 amino-terminal propeptide 35.06 μg/l, value at relapse 75.2 μg/l) 4.5 years after treatment. Values of serum C-terminal telopeptide and alkaline phosphatase of this patient were normal despite P1NP relapse. ConclusionsWe hence conclude that zoledronic acid is effective in inducing and maintaining biochemical remission and that procollagen type 1 amino-terminal propeptide is a better diagnostic and prognostic marker in PDB when compared to C-terminal telopeptide and alkaline phosphatase.

Localised melorheostosis

&lt;p class="abstract"&gt;&lt;span lang="EN-IN"&gt;Melorheostosis is a sclerosing bone dysplasia of unknown aetiology. Diagnosis is mainly based on a combination of clinical and imaging studies. The classical dripping candle wax picture on plain radiograph is diagnostic. We report a case of localized melorheostosis of a 14 year old boy on daily analgesics for two years for pain relief. Radiographs showed endosteal bone formation like dripping candle wax. Biopsy and decompression of the hyperostosis was done. However biopsy did not relieve his symptoms. Based on literature survey he was given a single infusion of zoledronic acid. This gave dramatic relief in pain.&lt;/span&gt;&lt;/p&gt;

Denosumab in treatment-naïve and pre-treated with zoledronic acid postmenopausal women with low bone mass: Effect on bone mineral density and bone turnover markers

PurposeTo compare denosumab-induced changes in lumbar spine (LS) and femoral neck (FN) bone mineral density (BMD), bone markers and free soluble receptor activator of nuclear factor kappaB ligand (sRANKL) between treatment naïve postmenopausal women with low bone mass (naïve group) and those who were previously treated with a single zoledronic acid infusion (post-Zol group). ProceduresProcollagen type 1N-terminal propeptide (P1NP), C-terminal cross-linking telopeptide of type 1 collagen (CTx) and sRANKL levels were measured in serum samples obtained at baseline and 3, 6 and 12months after denosumab initiation. LS and FN BMD were measured at baseline and 12months. ResultsLS and FN BMD increased significantly in both naïve and post-Zol group (p<0.001 and p=0.025 vs. p<0.001 and p=0.017, respectively). Despite the higher P1NP and CTx levels in naïve patients at baseline (both p<0.001), denosumab caused comparable decreases in both groups at month 3, which returned to post-Zol group baseline levels at month 6 and 12 in all patients. Similarly, sRANKL levels decreased significantly at month 3 in both groups and returned to baseline levels at months 6 and 12. ConclusionsIn patients previously treated with zoledronic acid, sequential denosumab treatment is effective in terms of BMD increases and bone turnover suppression. Despite the lower baseline levels in patients pre-treated with zoledronic acid, bone markers are similarly decreased in both groups following denosumab administration and maintain their reversibility. Denosumab reversibly suppresses endogenous free sRANKL levels in both naïve and zoledronic acid pre-treated patients.

Reduction in the Risk of Clinical Fractures After a Single Dose of Zoledronic Acid 5 Milligrams

Annual infusions of zoledronic acid 5 mg over 3 years have been shown to reduce fracture incidence. There is now evidence that the effects of a single dose of zoledronic acid on bone mineral density and bone turnover last for much more than a year. Whether this is associated with sustained fracture prevention is not known. The objective of the study was to assess fracture incidence after only 1 infusion of zoledronic acid. The design of the study included post hoc analysis of subgroups of subjects from 2 trials, who received only 1 study infusion. The study included multicenter, randomized controlled trials. A total of 1367 subjects from HORIZON-PFT and HORIZON-RFT studies who received only 1 of the planned annual infusions participated in the study. The intervention of the study consisted of 1 infusion of zoledronic acid or placebo. Clinical fracture was the main outcome measure of the study. Mean follow-up period was 1.5 years. In patients who received only a single infusion, there was a 32% reduction in clinical fracture comparing zoledronic acid with placebo over 3 years of follow-up (95% confidence interval 2-53%, P = .04), comparable with the fracture reduction seen in those who had 3 or more annual infusions (34%; 95% confidence interval, 23-43%, P < .0001). New morphometric vertebral fractures were reduced by 68% in the single-infusion group (P = .004). The between-group differences in total hip bone mineral density at 3 years were 3.8% in those receiving 1 infusion and 6.2% in those receiving 3 infusions. In this post hoc analysis based on postrandomization subgroups, fracture risk appears to be reduced for more than 1 year after a single infusion of zoledronic acid. Prospective studies designed to assess this possibility are now warranted.

Zoledronic acid reduces knee pain and bone marrow lesions over 1 year: a randomised controlled trial

ObjectivesTo compare the effect of a single infusion of zoledronic acid (ZA) with placebo on knee pain and bone marrow lesions (BMLs).MethodsAdults aged 50–80 years (n=59) with clinical knee osteoarthritis...

Vitamin D Reduces Musculoskeletal Pain After Infusion of Zoledronic Acid for Postmenopausal Osteoporosis

The acute-phase response (APR) is a frequent occurrence after infusion of zoledronic acid and is caused by activation of γδ T cells. Vitamin D receptor is expressed in immune cells, and vitamin D has immunomodulatory properties. The aim of this prospective study was to test the effect of vitamin D (cholecalciferol) on the incidence of APR and intensity of pain in women undergoing infusion of zoledronic acid for postmenopausal osteoporosis. 60 women were enrolled and randomized into two groups. At baseline, 30 women received an oral bolus of cholecalciferol (300,000IU), while another 30 women received placebo. On day 5 both groups were treated with a single infusion of zoledronic acid (5mg) and received a daily supplementation of calcium (1,000mg) and vitamin D (800IU). Patients were clinically evaluated and inflammatory markers were assayed before zoledronic acid administration and every 24h for the following 2days. The onset of APR has been defined by the occurrence of fever or at least one of the typical symptoms, such as musculoskeletal pain after zoledronic acid infusion. Intensity of pain was measured by a one-dimensional scale (0=no pain, 10=unbearable pain). APR developed in 66.6% of patients, with no significant difference between groups. The vitamin group experienced less musculoskeletal pain [median 1 (0-4) vs. 2 (1-8), P<0.05] and exhibited lower inflammatory markers (P<0.005 vs. placebo). Our data demonstrate that cholecalciferol at a dose of 300,000IU reduces the intensity of musculoskeletal pain after infusion of zoledronic acid for postmenopausal osteoporosis.

Prolonged Hypocalcemia After Zoledronic Acid in a Patient With Metastatic Prostate Carcinoma: Did Zoledronic Acid Trigger Osteoblastic Activity and Avid Calcium Uptake?

Because the inhibition of bone resorption also reduces therelease of calcium from the bone mineral matrix, bisphosphonatesalso are used to treat hypercalcemia.Here we describe a man with prostate cancer and extensiveskeletal osteoblastic metastasis who presented with prolonged,recalcitrant hypocalcemia in a peak-trough pattern after a singleinfusion of zoledronic acid (ZA). We postulate that ZA triggeredosteoblastic activity that led to avid calcium uptake and subse-quent hypocalcemia.

A Single Infusion of Zoledronic Acid Produces Sustained Remissions in Paget Disease: Data to 6.5Years

A Single Infusion of Zoledronic Acid Produces Sustained Remissions in Paget Disease: Data to 6.5Years

Post hoc analysis of a single IV infusion of zoledronic acid versus daily oral risedronate on lumbar spine bone mineral density in different subgroups with glucocorticoid-induced osteoporosis

This study summarizes the treatment effect of zoledronic acid infusion on lumbar spine bone mineral density in different subgroups with glucocorticoid-induced osteoporosis. Zoledronic acid is significantly more effective than risedronate in increasing lumbar spine (LS) bone mineral density (BMD) in both prevention and treatment of glucocorticoid-induced osteoporosis. Introduction In patients on glucocorticoids, a single zoledronic acid infusion significantly increased BMD versus daily oral risedronate. We assessed treatment effect on LS BMD in different patient subgroups at month 12 that contributed to the risk of osteoporosis in addition to glucocorticoids. Methods Patients randomized to a single IV infusion of zoledronic acid 5 mg or risedronate (5 mg/day) and stratified based on glucocorticoids duration [treatment (>3 months) and prevention (≤ 3 months) subpopulations]were subgrouped by age; gender; menopausal status in women; dose and duration of prednisone during the trial; and baseline serum 25-OH vitamin D, LS BMD T-score, creatinine clearance, and concomitant medication use. Results At month 12, zoledronic acid significantly increased LS BMD versus risedronate in patients ≤ 74 years (P<0.05) in the treatment and 65-74 years (P = 0.0008) in the prevention subpopulation. At month 12, zoledronic acid significantly increased LS BMD versus risedronate in both subpopulations irrespective of gender (all P<0.05), cumulative prednisone dose (all P<0.01), and postmenopausal status (all P<0.05). In premenopausal women, in both subpopulations, zoledronic acid significantly increased total hip BMD (all P<0.05) versus risedronate at month 12 but not LS BMD. Osteoporotic patients in the prevention (P=0.0189) and osteopenic patients in the treatment subpopulation (P=0.0305) showed significant LS BMD increases with zoledronic acid versus risedronate at month 12. Conclusions This post hoc analysis suggests that zoledronic acid is significantly more effective than risedronate in increasing LS BMD in prevention and treatment of glucocorticoid-induced osteoporosis across a wide range of patients.

A single bisphosphonate infusion does not accelerate fracture healing in high tibial osteotomies

Background Bisphosphonates increase the callus size and strength in animal fracture studies. In a human non-randomized pilot study of high tibial osteotomies in knee osteoarthritis, using the hemicallotasis (HCO) technique, bisphosphonates shortened the healing time by 12 days. In the present randomized study, we wanted to determine whether a single infusion of zoledronic acid reduces the time to clinical osteotomy healing. Results from the same trial, showing improved pin fixation with zoledronate, have been published separately.Methods 46 consecutive patients (aged 35–65 years) were operated. At 4 weeks postoperatively, the patients were randomized to an intravenous infusion of either zoledronic acid or sodium chloride. Dual-energy X-ray absorptiometry (DEXA) was performed 10 weeks postoperatively. Radiographs were taken at 10 weeks and every second week until there was radiographic and clinical healing. Healing was evaluated blind, with extraction of the external fixator as the endpoint. At 1.5 years, an additional radiograph was taken and the hip-knee-ankle (HKA) angle measured to evaluate whether correction had been retained.Results All osteotomies healed with no difference in healing time between the groups (77 (SD 7) days). Bone mineral density and bone mineral content, as assessed with DEXA, were similar between the groups. Radiographically, both groups had retained the acquired correction at the 1.5-year follow-up.Interpretation In this randomized comparison, a single infusion of zoledronic acid increased the pin fixation of the external frame but did not shorten the healing time. In both groups, the external fixator was extracted almost 2 weeks earlier than in previous studies. The early extraction did not cause a loss of correction in either group.

A single infusion of zoledronic acid produces sustained remissions in paget disease: Data to 6.5 years

Two trials have shown that a single 5-mg infusion of zoledronic acid achieves much higher response rates in Paget disease of bone than risedronate. The duration of this effect is unknown. We have conducted an open follow-up of responders from the two trials (152 originally treated with zoledronic acid, 115 with risedronate) out to 6.5 years without further intervention. Endpoints were times to relapse (ie, return of serum total alkaline phosphatase activity to within 20% of the pretreatment value) or loss of response (response = normalization of alkaline phosphatase or 75% or greater reduction in its excess). Bone turnover markers were lower in the zoledronic acid group throughout follow-up, with mean alkaline phosphatase (ALP) remaining within the reference range in these patients, whereas the mean in the risedronate group was above normal from 1 year. Relapse rates were substantially greater in the risedronate group (23 of 115, 20%) than in those treated with zoledronic acid (1 of 152, 0.7%, p < .001), and loss of response occurred in 19 (12.5%) zoledronic acid patients compared with 71 (62%) risedronate patients (p < .0001). Risk ratios for relapse and loss of response in zoledronic acid patients were 0.02 [95% confidence interval (CI) 0.00-0.18] and 0.12 (95% CI 0.07-0.19), respectively. Changes from baseline in quality of life, assessed using SF-36 scores, were more positive in the zoledronic acid group across the follow-up period (p = .01). Bone markers at 6 months were predictive of response duration. These data demonstrate an unprecedented duration of remission of Paget disease following treatment with zoledronic acid, accompanied by an improved quality of life.

Effects of intravenous zoledronic acid plus subcutaneous teriparatide [rhPTH(1–34)] in postmenopausal osteoporosis

Clinical data suggest concomitant therapy with bisphosphonates and parathyroid hormone (PTH) may blunt the anabolic effect of PTH; rodent models suggest that infrequently administered bisphosphonates may interact differently. To evaluate the effects of combination therapy with an intravenous infusion of zoledronic acid 5 mg and daily subcutaneous recombinant human (rh)PTH(1-34) (teriparatide) 20 µg versus either agent alone on bone mineral density (BMD) and bone turnover markers, we conducted a 1-year multicenter, multinational, randomized, partial double-blinded, controlled trial. 412 postmenopausal women with osteoporosis (mean age 65 ± 9 years) were randomized to a single infusion of zoledronic acid 5 mg plus daily subcutaneous teriparatide 20 µg (n = 137), zoledronic acid alone (n = 137), or teriparatide alone (n = 138). The primary endpoint was percentage increase in lumbar spine BMD (assessed by dual-energy X-ray absorptiometry [DXA]) at 52 weeks versus baseline. Secondary endpoints included change in BMD at the spine at earlier time points and at the total hip, trochanter, and femoral neck at all time points. At week 52, lumbar spine BMD had increased 7.5%, 7.0%, and 4.4% in the combination, teriparatide, and zoledronic acid groups, respectively (p < .001 for combination and teriparatide versus zoledronic acid). In the combination group, spine BMD increased more rapidly than with either agent alone (p < .001 versus both teriparatide and zoledronic acid at 13 and 26 weeks). Combination therapy increased total-hip BMD more than teriparatide alone at all times (all p < .01) and more than zoledronic acid at 13 weeks (p < .05), with final 52-week increments of 2.3%, 1.1%, and 2.2% in the combination, teriparatide, and zoledronic acid groups, respectively. With combination therapy, bone formation (assessed by serum N-terminal propeptide of type I collagen [PINP]) increased from 0 to 4 weeks, declined minimally from 4 to 8 weeks, and then rose throughout the trial, with levels above baseline from 6 to 12 months. Bone resorption (assessed by serum β-C-telopeptide of type I collagen [β-CTX]) was markedly reduced with combination therapy from 0 to 8 weeks (a reduction of similar magnitude to that seen with zoledronic acid alone), followed by a gradual increase after week 8, with levels remaining above baseline for the latter half of the year. Levels for both markers were significantly lower with combination therapy versus teriparatide alone (p < .002). Limitations of the study included its short duration, lack of endpoints beyond DXA-based BMD (e.g., quantitative computed tomography and finite-element modeling for bone strength), lack of teriparatide placebo, and insufficient power for fracture outcomes. We conclude that while teriparatide increases spine BMD more than zoledronic acid and zoledronic acid increases hip BMD more than teriparatide, combination therapy provides the largest, most rapid increments when both spine and hip sites are considered.

A single dose zoledronic acid enhances pin fixation in high tibial osteotomy using the hemicallotasis technique. A double-blind placebo controlled randomized study in 46 patients

IntroductionBisphosphonates have been shown to reduce osteoclastic activity and enhance pin fixation in both experimental and clinical studies. In this prospective, randomized study of high tibial osteotomy using the hemicallotasis (HCO) technique, we evaluate whether treatment by one single infusion of zoledronic acid can enhance the pin fixation. Materials and methods46 consecutive patients (35–65 years) were operated on for knee osteoarthritis by the HCO technique. After the osteotomy, two hydroxyapatite-coated pins were inserted in the metaphyseal bone and two non-coated pins in the diaphyseal bone. The insertion torque was measured by a torque force screw driver. Four weeks postoperatively, the patients were randomized to either one infusion of zoledronic acid or sodium chloride intravenously. At time for removal of the pins, the extraction torque forces of the pins were measured. ResultsAll osteotomies healed and no difference was found in time to healing. The mean extraction torque force in the non-coated pins in the diaphyseal bone was doubled in the zoledronic treated group (4.5 Nm, SD 2.1) compared to the placebo group (2.4 (SD 1.0, p<0.0001). The mean extraction torque forces of the hydroxyapatite-coated pins in the metaphyseal bone were similar in the zoledronic acid group (4.7 Nm, SD 1.3) and in the placebo group (4.0 Nm, SD 1.3). DiscussionA single infusion of zoledronic acid improved twofold the fixation of non-coated pins in diaphyseal bone. Bisphosphonates might be an alternative to hydroxyapatite-coated pins in nonosteoporotic bone.

Single infusion of zoledronic acid to prevent androgen deprivation therapy‐induced bone loss in men with hormone‐naive prostate carcinoma

Androgen-deprivation therapy (ADT) decreases bone mineral density (BMD) and increases fracture risk in patients with prostate carcinoma. The authors investigated the effectiveness of a single infusion of zoledronic acid initiated subsequent to ADT on BMD with hormone-naive prostate carcinoma. Forty men received either a single infusion of zoledronic acid (4 mg intravenously on Day 1) or no infusion during ADT. BMD of the proximal femur and posteroanterior lumbar spine was measured by dual-energy x-ray absorptiometry and urinary N-telopeptide (u-NTx) at 6 and 12 months. At baseline, the overall BMDs demonstrated no significant difference in lumbar spine and hip regions. At 6 months, mean (+/-standard error) BMD of the posteroanterior lumbar spine decreased 4.6%+/-1.0% in control patients and increased 5.1%+/-1.2% in patients receiving zoledronic acid, a significant difference (P=.0002). At 12 months, the change in BMD between the 2 groups was statistically significantly different at the lumbar region (P=.0004), indicating that zoledronate preserved BMD. For u-NTx, bone turnover was statistically significantly decreased in the zoledronate group compared with controls at 6 months (P<.0001), but returned to pretreatment levels at 12 months in the zoledronate group. Bone loss begins at 6 months with ADT. A single infusion of zoledronic acid in patients receiving ADT reduces bone mineral loss and maintains BMD at least at 12 months during ADT. Further study is needed to determine the best dosing schedule to prevent ADT-induced bone loss in men with hormone-naive prostate carcinoma.

SINGLE INFUSION OF ZOLEDRONIC ACID TO PREVENT ANDROGEN- DEPRIVATION THERAPY-INDUCED BONE LOSS IN MEN WITH HORMONE-NAÏVE PROSTATE CANCER

BACKGROUND: Androgen-deprivation therapy (ADT) decreases bone mineral density (BMD) and increases fracture risk in patients with prostate carcinoma. The authors investigated the effectiveness of a single infusion of zoledronic acid initiated subsequent to ADT on BMD with hormone-naive prostate carcinoma. METHODS: Forty men received either a single infusion of zoledronic acid (4 mg intravenously on Day 1) or no infusion during ADT. BMD of the proximal femur and posteroanterior lumbar spine was measured by dual-energy x-ray absorptiometry and urinary N-telopeptide (u-NTx) at 6 and 12 months. RESULTS: At baseline, the overall BMDs demonstrated no significant difference in lumbar spine and hip regions. At 6months, mean (� standard error) BMD of the posteroanterior lumbar spine decreased 4.6% � 1.0% in control patients and increased 5.1% � 1.2% in patients receiving zoledronic acid, a significant difference (P ¼ .0002). At 12 months, the change in BMD between the 2 groups was statistically significantly different at the lumbar region (P ¼ .0004), indicating that zoledronate preserved BMD. For u-NTx, bone turnover was statistically significantly decreased in the zoledronate group compared with controls at 6 months (P < .0001), but returned to pretreatment levels at 12 months in the zoledronate group. CONCLUSIONS: Bone loss begins at 6 months with ADT. A single infusion of zoledronic acid in patients receiving ADT reduces bone mineral loss and maintains BMD at least at 12 months during ADT. Further study is needed to determine the best dosing schedule to prevent ADT-induced bone loss in men with hormone-naive prostate carcinoma. Cancer 2009;115:3468–74. V C 2009 American Cancer Society.

The Effect of a Single Infusion of Zoledronic Acid on Early Implant Migration in Total Hip Arthroplasty

Aseptic loosening is the most frequent cause of implant failure in total hip arthroplasty. While a direct link between aseptic loosening and periprosthetic bone loss remains elusive, there is plentiful evidence for a close association with early implant migration. The present trial was primarily designed to evaluate whether a single infusion of 4 mg of zoledronic acid prevented early implant migration in patients with osteonecrosis of the femoral head. Fifty patients were consecutively enrolled to receive either zoledronic acid or saline solution after cementless total hip arthroplasty. Radiographs, biochemical parameters of bone turnover, and the Harris hip-rating score were determined preoperatively and at each follow-up examination at seven weeks, six months, one year, and yearly thereafter. The median follow-up period was 2.8 years. We found a significant subsidence of the stem of up to a mean (and standard deviation) of -1.2 +/- 0.6 mm at two years within the control group, and the cups had a mean medialization of 0.6 +/- 1.0 mm and a mean cranialization of 0.6 +/- 0.8 mm (p < 0.001). Treatment with zoledronic acid effectively minimized the migration of the cups in both the transverse and the vertical direction (mean, 0.15 +/- 0.6 mm and 0.06 +/- 0.6 mm, respectively; p < 0.05), while only a trend to decreased subsidence of the stem was detected. Finally, the Harris hip score rapidly increased over time in both treatment groups, although this increase was significantly more pronounced in the zoledronate-treated group than in the control group (analysis of variance, p = 0.008). A single infusion of zoledronic acid shows promise in improving initial fixation of a cementless implant, which may improve the clinical outcome of total hip arthroplasty in patients with osteonecrosis of the femoral head.