Bisphosphonate-related Osteonecrosis of the Jaws: An Update on Clinical, Pathological and Management Aspects

Bisphosphonate-related osteonecrosis of the jaws (BRONJ) is mainly observed in patients with multiple myeloma and bone metastasis from solid tumors receiving iv bisphosphonate therapy. The reported incidence of BRONJ is significantly higher with the iv preparations zoledronic acid and pamidronate while the risk appears to be minimal for patients receiving oral bisphosphonates. Currently available published incidence data for BRONJ are based on retrospective studies and estimates of cumulative incidence range from 0.8 to 12%. The mandible is more commonly affected than the maxilla (2:1 ratio), and 60–70% of cases are preceded by a dental surgical procedure. The signs and symptoms that may occur before the appearance of clinical evident osteonecrosis include changes in the health of periodontal tissues, non-healing mucosal ulcers, loose teeth and unexplained soft-tissue infection. Although the definitive role of bisphosphonates remains to be elucidated, the inhibition of physiologic bone remodeling and angiogenesis by these potent drugs impairs the regenerative capacity of the bone causing the development of BRONJ. Tooth extraction as a precipitating event is a common observation. The significant benefits that bisphosphonates offer to patients clearly surpass the risk of potential side effects; however, any patient for whom prolonged bisphosphonate therapy is indicated, should be provided with preventive dental care in order to minimize the risk of developing this severe condition. This article provides an update review of current knowledge about clinical, pathological and management aspects of BRONJ.     

行气活血补肾壮骨方在双膦酸盐药物休假期患者的临床观察

摘要：目的：观察益气活血补肾壮骨方在骨质疏松症(气滞血瘀型)患者双膦酸盐药物休假期的临床疗效和不良反应等。方法：将本院2019年12月—2021年7月就诊120例气滞血瘀型骨质疏松症双膦酸盐药物休假期患者按照随机数字表均分为两组。对照组予钙片、阿法骨化醇胶囊、金天格治疗,研究组予钙片、阿法骨化醇胶囊加用益气活血补肾壮骨方治疗。治疗6个月后,比较两组患者骨代谢、细胞因子、骨密度、 健康调查简表(SF-36评分)、脆性骨折发生率、骨折风险评估、中医证候积分、疗效和不良反应等。结果：治疗前两组各项指标比较差异无统计学意义(p>0.05)。治疗后研究组骨代谢低于对照组（BGP25.69±4.07vs26.37±4.16ng/mL、PINP35.79±7.38vs37.02±8.12ng/mL、CTX0.85±0.14vs1.26±0.21mmol/L、TRACP8.93±1.26vs13.06±2.59u/L）,细胞因子(IL-1:26.36±3.07vs23.75±2.93pg/mL、IL-6:82.71±6.25vs78.62±9.08pg/mL、TNF-α5.03±1.02vs3.81±1.09ng/L)高于对照组,差异有统计学意义（p<0.05）。研究组SF-36评分(87.46±8.32vs70.62±6.59)、西医有效率(86%vs80%)、中医症候积分(23.46±5.32vs21.62±4.59)、中医疗效有效率(84%vs76%)高于对照组,左股骨颈BMD(0.68±0.05vs0.70±0.06g/cm2),脆性骨折发生率(2%vs8%)、骨折风险评估(1.49±0.32vs2.63±0.47)低于对照组,但差异无统计学意义(p>0.05)。结论：益气活血补肾壮骨方联合钙片、阿法骨化醇胶囊可改善双膦酸盐药物假期患者(气滞血瘀型)骨代谢水平,抑制骨吸收和炎性因子水平、促进骨形成、提高骨密度,降低脆性骨折发生率和骨折风险,提高中医症候积分、生活质量,从而提高疗效,疗效水平与金天格相当。     

Management of osteoporosis in the elderly

ABSTRACT

Background: Osteoporosis is predominantly a condition of the elderly, and the median age for hip fracture in women is approximately 83 years. Osteoporotic fracture risk is multifactorial, and often involves the balance between bone strength and propensity for falling.

Objective: To present an overview of the available evidence, located primarily by Medline searches up to April, 2009, for the different management strategies aimed at reducing the risk of falls and osteoporotic fractures in the elderly.

Results: Frailty is an independent predictor of falls, hip fractures, hospitalisation, disability and death in the elderly that is receiving increasing attention. Non-pharmacological strategies to reduce fall risk can prevent osteoporotic fractures. Exercise programmes, especially those involving high doses of exercise and incorporating balance training, have been shown to be effective. Many older people, especially the very elderly and those living in care institutions, have vitamin D inadequacy. In appropriate patients and given in sufficient doses, vitamin D and calcium supplementation is effective in reducing both falls and osteoporotic fractures, including hip fractures. Specific anti-osteoporosis drugs are underused, even in those most at risk of osteoporotic fracture. The evidence base for the efficacy of most such drugs in the elderly is incomplete, particularly with regard to nonvertebral and hip fractures. The evidence base is perhaps most complete for the relatively recently introduced drug, strontium ranelate. Non-adherence to treatment is a substantial problem, and may be exacerbated by the requirements for safe oral administration of bisphosphonates.

Conclusion: Evidence-based strategies are available for reducing osteoporotic fracture risk in the elderly, and include exercise training, vitamin D and calcium supplementation, and use of evidence-based anti-osteoporotic drugs. A positive and determined approach to optimising the use of such strategies could reduce the burden of osteoporotic fractures in this high-risk group.     

药物相关性颌骨坏死治疗方法的研究进展

药物相关性颌骨坏死是患者使用抗骨吸收或抗血管生成药物导致的并发症,破坏了口腔卫生,影响患者饮食、语音功能,降低生活质量。对MRONJ患者最恰当的治疗策略还未达成共识。本文就近年来药物相关性颌骨坏死的分期及辅助治疗方法的研究进展作一综述。     

Bisphosphonate-associated osteonecrosis of the auditory canal

Only rare cases of osteonecrosis of the auditory canal associated with bisphosphonates, have been published. Our results confirm that similar reports can also be encountered in databases of adverse drug reactions.     

双磷酸盐相关性颌骨坏死的循证治疗:附3例报道

目的:探讨双磷酸盐相关性颌骨坏死的循证治疗。方法:针对3例双磷酸盐用药患者出现的拔牙创不愈、牙周肿痛、溢脓等症状,提出临床问题,检索收集并评价相关证据,帮助制订治疗方案。结果:共纳入相关文献39篇,结果显示①双磷酸盐相关性颌骨坏死的致病机制不明;诊断标准普遍参照美国口腔颌面外科医师协会的临床指南。②治疗方案为早期有骨坏死或暴露而无明显感染时,先行抗感染、镇痛等非手术治疗;感染症状复发时,行局部清创术;出现大段骨坏死或病理性骨折时,行大范围骨切除。③组织病理学诊断标准尚未建立;影像学检查有助于早期诊断和牙槽骨手术前评估。④停药并不能缓解症状和进程,但在清创和牙槽骨手术期间有利于伤口愈合,是否停药由医患双方协商确定。根据以上证据,对3例患者先行保守治疗,效果不佳后行局部清创术,随访6~12个月,疗效良好。结论:双磷酸盐相关性颌骨坏死是近年新出现的疾病。目前致病机制不明,诊断和治疗方法未统一。循证治疗可制定合理方案,有效提高治疗效果和生存质量。