Radical surgical treatment of bisphosphonate related osteonecrosis of the jaw

We describe a case of a 64-year-old female diagnosed with multiple myeloma in 2001. She was treated with pamidronate and subsequently zolodronic acid before developing spontaneous bisphosphonate related osteonecrosis (BRONJ) of the left maxilla in December 2008. Over the next two years the BRONJ was treated conservatively but gradually became more symptomatic. About three years after her last dose of zolodronic acid with her symptoms increasing, she underwent radical surgical excision of all diseased bone and flap reconstruction. The patient is now six months postoperative and symptom free.     

The effect of vitamin D and bisphosphonate on fracture healing: An experimental study

BackgroundThe aim of the study was to evaluate the effects of the using bisphosphonate, vitamin D, and a combination of bisphosphonate and vitamin D on fracture healing, by comparison of radiological and histological findings of the study groups and a control group.MethodsA total of 24 rats were randomly divided into 4 groups. A mid-third fracture was created in the femur of all rats. Saline was administered to Group A, bisphosphonate (Alendronate) to Group B, bisphosphonate (Alendronate) + vitamin D (Calcitriol) to Group C and vitamin D (Calcitriol) to Group D. All preparations were administered orally for 28 days.ResultsNo statistically significant difference was determined between the groups in respect of the effect on fracture healing according to radiological findings. The histological findings of fracture healing showed Groups B and C to be significantly more advanced than Group A (p = 0.017, p = 0.009). However no significant difference was found in Group D comparison with Group A (p = 0.224).ConclusionAccording to the histological findings, advanced fracture healing was seen in the groups administered with bisphosphonate or combined bisphosphonate and vitamin D compared to the use of vitamin D alone and the control group. It was concluded that bisphosphonate treatment combined with vitamin D can be used safely without any negative effect on fracture healing.     

Effects of neridronic acid on osteoclasts derived by physiological dual-cell cultures

Increased osteoclastic activity is observed in many osteopathic disorders - including postmenopausal osteoporosis, Paget's disease, primary bone tumours, lytic bone metastases, multiple myeloma and rheumatoid arthritis - that involve increased bone resorption and a loss of bone mass. Bisphosphonates are highly effective inhibitors of bone resorption that selectively affect the osteoclasts. The aim of this study was to obtain more information about the mechanism of action of bisphosphonates such as neridronic acid using a dual-cell culture model. As a model of osteoclastogenesis we used a murine monocyte/macrophage cell line RAW 264.7 type CRL 2278 co-cultured with murine osteoblasts. The monocyte-osteoblast system allows physiological experimentation of bone anti-resorption drugs, simulating bone turnover in pathologies such as osteoporosis. The direct actions of neridronic acid on cell proliferation and functionality in the co-culture model were examined using tartrate-resistant acid phosphatase (TRAP) assay, immunohistochemical localization of actin, and transmission and scanning electron microscopy (SEM). Results showed that the percentage of TRAP-positive cells, an early marker of osteoclastic differentiation, was significantly higher in control cultures than in co-cultures treated with variable concentrations of neridronic acid. Neridronic acid induced dramatic morphological changes, characterized by the loss of the ruffled border. The actin ring associated with the plasma membrane of the cells treated with neridronic acid was shown to break down. The tissue-specific targeting of neridronic acid to bone mineral suggests that it may inhibit bone resorption by direct effects on osteoclasts or other bone cells in the immediate microenvironment of the osteoclasts. From our study, we conclude that structural alterations induced by neridronic acid in our co-culture system lead to decreased osteoclast function. This may encourage the use of neridronic acid to reduce bone resorption in the therapy of demineralizing metabolic bone disorders.     

Atypical femoral fractures after anti-osteoporotic medication: a Korean multicenter study

Purpose

Increasing numbers of atypical femoral fractures have been reported among long-term bisphosphonate users. We evaluated clinical characteristics of atypical femoral fractures throughout Korean multicenter studies.

Methods

We retrospectively analysed the bone mineral density, prodromal symptoms before femoral fracture, and medication history of osteoporosis in 76 cases of atypical femoral fracture.

Results

The mean age of cases was 71.4 ± 8.8 (range, 43–89) years old. The mean follow-up period after the fracture operation was 24.5 ± 12.9 (range, 12–79) months. BMI was 23.2 ± 3.0 on average. The mean BMD of femur was −1.9 ± 1.4 (range, −4.8 to 1.3). Prodromal symptoms including thigh pain before femoral fracture appeared in 22 (28.9 %) of 76 patients. All patients included in the study used bisphosphonate. The duration of taking bisphosphonate before fracture was 36.8 ± 50.8 (one–204 months) months. Fifty-seven (75 %) of 76 patients were taking the medication for more than three years. Delayed union occurred in 43 (56.5 %) of 76 patients. Delayed union was defined as a fractured bone that did not completely heal within six months of injury. The group of having taken anti-osteoporotic medication for more than three years showed relatively longer union period compared to that for a shorter period medication group (4.8 ± 2.5 months vs 9.3 ± 3.7 months, p = 0.017). The delayed union developed in 43 (56.5 %) of 76 patients and showed a significantly higher incidence in the group with long-term therapy (five/43 vs 38/43, p = 0.021). The bilateral femoral fractures developed in 23 (30.2 %) of 76 patients and showed a high incidence in the group medicated more than three years (two/23 vs 21/23, p = 0.039).

Conclusions

The longer bisphosphonates are used, the more the cases of delayed union and the more frequent the development of bilateral fractures following unilateral fractures. With regard to the delayed union, the methods of the acceleration of fracture healing may be beneficial in atypical femoral fracture patients who had been receiving long-term bisphosphonates therapy. Careful observation is required for contra-lateral femurs due to a high incidence of bilateral atypical femoral fractures.     

Prostate-Specific Antigen Kinetics and Outcomes in Patients with Bone Metastases from Castration-Resistant Prostate Cancer Treated with or Without Zoledronic Acid

Background

Zoledronic acid (ZOL) is a standard therapy for the prevention of skeletal-related events (SREs) in patients with castration-resistant prostate cancer (CRPC). Although prostate-specific antigen (PSA) is an established marker for monitoring prostate cancer patients, correlations between PSA and disease outcomes during ZOL therapy are unclear.

Objective

To evaluate the relationships among PSA kinetics, bone-directed therapy with ZOL, and clinical outcomes in men with bone metastases from CRPC using a ZOL phase 3 trial database.

Design, setting, and participants

Exploratory analyses from a phase 3 trial in men with bone metastases from CRPC (n = 643) randomized to ZOL or placebo every 3 wk.

Outcome measurements and statistical analysis

PSA levels during the first 3 mo of the study were evaluated in linear and logarithmic (log) models stratified using prognostic factors established in a ZOL phase 3 trial and a CRPC nomogram. Relative risks of SREs, bone disease progression (BDP), and death were calculated per 1 log (nanograms per milliliter) PSA increase. Baseline PSA models used the study median (PSA: 77.3 ng/ml) as the high/low cut-off point.

Results and limitations

A total of 202 placebo- and 434 ZOL-treated patients were assessable. In both groups, PSA increases correlated with significantly increased risks of death, BDP, and first SRE. In the placebo and ZOL groups, associated increases in risk per 1 log (nanograms per milliliter) PSA increase were 29% (p < 0.0001) and 10% (p < 0.0074), respectively, for BDP, and 24% (p = 0.0010) and 13% (p = 0.0079), respectively, for first SRE. Limitations include the retrospective nature of these analyses and the potential confounding effects of concurrent antineoplastic therapies.

Conclusions

PSA is an important prognostic tool for survival in patients with bone metastases from CRPC, and these analyses show that PSA is also prognostic for BDP and SREs regardless of bone-targeted therapy.     

Salud ósea en pacientes con cáncer de próstata

ContextIn patients with prostate cancer, bone health is compromised by advanced age at diagnosis, androgen suppression treatments and the developmentofbone metastases. In this paper the medical literature is reviewed in order to update the state of the art on their incidence, prevention and management.Evidence acquisitionA literature review about bone involvement in patients with prostate cancer in different clinical settings is performed.Synthesis of the evidenceDecreased bone mineral density is higher in patients diagnosed of prostate cancer before starting treatment than in healthy men with the same age. During the first year of treatment, a severe loss bone density is reported due to androgen suppression therapy. From then on, loss bone density seems to slow down, persisting at long-term. It is important to know the starting point and the dynamics of loss bone in order to prevent its progression. The skeletal events have an important impact on quality of life in patients with prostate cancer. Both Denosumab and Zoledronic Acid have proven effective in reducing loss bone.ConclusionsThe prevention and management of bone involvement in patients with prostate cancer is critical to quality of life in these patients and requires an individualized approach. Before starting a prolonged androgen deprivation, baseline risk of fracture should be evaluated in order to adopt the proper protective measures. In patients with metastases, early treatments reducing the risk of bone events should be taken into account.     

南京地区34家医院2010-2012年双膦酸盐类药物应用分析

目的:了解双膦酸盐类药物的使用状况及趋势。方法:采用世界卫生组织推荐的限定日剂量为指标的分析方法,对南京地区34家医院2010-2012年的双膦酸盐类药物的销售金额、用药频度(DDDs)和日均费用(DDC)等进行统计、分析。结果:双膦酸盐类药物销售金额和DDDs逐年增加,销售金额平均增幅达25.5%,DDDs以年均14%的速度增长,DDC处于稳中略降的态势。双膦酸盐氯屈膦酸由于口服方便、价格便宜,市场占有率依然较高,2012年销售金额占10.65%。临床安全性和疗效方面更佳的第三代双膦酸盐占据了主要市场,以唑来膦酸(2012年销售金额占63.81%)和阿仑膦酸钠(2012年销售金额占12.59%)为主。结论:双膦酸盐类药物在骨吸收相关性疾病中的应用逐渐受到重视,第二代和第三代双膦酸盐已经占据了主要市场。