Osteonecrosis of the jaw induced by orally administered bisphosphonates: incidence, clinical features, predisposing factors and treatment outcome

Summary Osteonecrosis of the jaw (ONJ) is a well-known devastating side effect of bisphosphonate therapy for cancer. Several ONJ cases of patients using oral bisphosphonates have been reported in the literature. The present study analyzed the clinical features, predisposing factors, and treatment outcome of 11 patients with oral bisphosphonates-related ONJ. Introduction and hypothesis Osteonecrosis of the jaw (ONJ) is a well-known side effect of parenteral bisphosphonates therapy. Although ONJ has been reported in patients using oral bisphosphonates, documentation of this entity is sparse. It was hypothesized that the clinical features, predisposing factors, and treatment outcome of this population are different from those of oncologic patients. Methods This retrospective bi-central study involved 98 ONJ patients, 13 of whom were treated with oral bisphosphonates. Two patients were excluded because of previous use of intravenous bisphosphonates. The profiles of 11 patients were analyzed. Results The mean duration of alendronate use before developing ONJ was 4.1 years. ONJ was triggered by dental surgery in 9 patients and by ill-fitted dentures in 2. Heavy smokers were the most recalcitrant subjects. Among the nine patients with at least 6 months of follow-up, ONJ healed completely in three, partially in four, and not at all in two. Conclusions ONJ is a rare devastating side effect of oral bisphosphonates associated with patient morbidity and high financial burden. Clinicians must be aware of this entity and inform patients of the risks of dental surgery. The synergistic effect of smoking in the pathogenesis of ONJ should be further investigated.     

Bisphosphonate-induced Osteonecrosis of the Jaws: Review, Clinical Implications and Case Report

The introduction of bisphosphonates has increased in the last decade following their indication for metastatic bone diseases, osteoporosis, hypercalcaemia of malignancy and Paget’s disease. Although bisphosphonates have been used clinically for more than three decades there have been no documented long-term complications of their effects on the jaws until recently, where there is now growing evidence of the influence of bisphosphonates on osteonecrosis of the jaws. The aim of this paper is to report a case of this newly described complication, to review this phenomenon, including the clinical implications and to reiterate current clinical guidelines for management of patients in which bisphosphonate therapy is indicated. To the best of our knowledge this is the first reported case of bisphosphonate-induced necrosis of the jaw in South Africa.     

Osteonecrosis of the jaw and bisphosphonate treatment for osteoporosis

A potential side effect associated with bisphosphonates, a class of drugs used in the treatment of osteoporosis, Paget's disease and metastatic bone disease, is osteonecrosis of the jaw (ONJ). The incidence of ONJ in the general population is unknown; this rare condition also may occur in patients not receiving bisphosphonates. Case reports have discussed ONJ development in patients with multiple myeloma or metastatic breast cancer receiving bisphosphonates as palliation for bone metastases. These patients are also receiving chemotherapeutic agents that might impair the immune system and affect angiogenesis. The incidence or prevalence of ONJ in patients taking bisphosphonates for osteoporosis seems to be very rare. No causative relationship has been unequivocally demonstrated between ONJ and bisphosphonate therapy. A majority of ONJ occurs after tooth extraction. Furthermore, the underlying risk of developing ONJ may be increased in osteoporotic patients by comorbid diseases. Treatment for ONJ is generally conservative.     

A Randomized, Double-Blind, Placebo-Controlled Trial of Intravenous Zoledronic Acid in the Treatment of Thalassemia-Associated Osteopenia

Beta-thalassaemia major is associated with low bone mass and fractures. We conducted a 2 year randomized controlled trial of zoledronic acid 4 mg administered intravenously every 3 months or placebo in the treatment of β-thalassaemia-associated osteopenla. We recruited 23 subjects from 2 university hospitals with a T score of less than −1.0 at either the lumbar spine or hip, and 23 subjects completed the study (17 M, 6 F). Treatment groups did not differ significantly with respect to bone mineral density (BMD), age, height, weight and body mass index (BMI) at baseline. BMD was assessed at baseline, 12 months and 24 months by dual-energy X-ray absorptiometry (DXA) at the lumbar spine, femoral reek, total hip and total body. After two years average lumbar spine BMD was 8.9% greater (95%CI 2.3–15.5%, P = 0.011), average femoral neck BMD was 9.1% greater (95%CI 5.5–12.7%, P < 0.0001), average total hip BMD was 9.6% greater (95%CI 6.5–12.6%, P < 0.0001) and average total body BMD was 4.7% greater (95%CI 2.7–6.8%, P < 0.0001) in the treated group compared to placebo. The absolute change in BMD from baseline to 2 years and the annualized rate of change of BMD was significantly greater in treated patients at all four sites. Age, gender, height, weight and BMI did not interact with the effect of treatment and so unadjusted data was used. The serum total ALP decreased 45% by 12 months (P = 0.004) and urinary deoxypyridinoline/creatinine ratio decreased 47% by 3 months (NS). We conclude that zoledronic acid (4 mg i.v. 3 monthly) suppresses bone turnover and increases BMD in β-thalassaemia-associated osteopenia.     

唑来膦酸治疗糖皮质激素性骨质疏松症的临床观察

目的：观察唑来膦酸（密固达,5 mg/100 ml）治疗糖皮质激素性骨质疏松症（ GIO）患者的一年临床疗效、安全性及患者依从性。方法以8例糖皮质激素性骨质疏松症患者为观察对象,应用唑来膦酸,每年静滴一次5 mg/100 ml,同时口服钙尔奇D和阿法骨化醇胶丸0.25 ug,治疗前后采用双能X线骨密度仪,测定骨密度,观察骨密度变化情况及用药过程中及近一年出现的不良反应。结果8例患者治疗一年后腰椎、股骨颈及大转子部位骨密度较治疗前增加（P＜0.05）,无新骨折发生,有两例病人用药后三天出现发热及流感样症状,其他病人观察过程中,无不良反应发生。8例患者有1例患者已连续用药三次,3例患者已接受第二次给药,4例患者复查骨密度恢复正常后,暂缓用药。结论唑来膦酸治疗糖皮质激素性骨质疏松症可以增加骨密度、提高生活质量、减少骨折的发生,是一种安全有效、患者依从性较高的药物。     

The Effect of Zoledronic Acid on the Volume of the Fusion-Mass in Lumbar Spinal Fusion

Background

Few studies have explored the effects of bisphosphonates on bony healing in patients undergoing spinal fusion surgery. Most previous studies used animal models and found that bisphosphonate shows negative effects on spinal fusion consolidation. We intended to evaluate the effect of a single-dose of zoledronic acid on the volume of the fusion-mass in lumbar spinal fusion.

Methods

A retrospective review was carried out on 44 patients with symptomatic degenerative lumbar spinal stenosis who underwent one or two-level posterolateral fusion from January 2008 and January 2011. They were divided into 4 groups: group 1, autograft and zoledronic acid; group 2, allograft and zoledronic acid; group 3, autograft alone; and group 4, allograft alone. Functional radiography and three-dimensional computed tomography scans were used to evaluate and quantify the volume of the fusion-mass. The visual analog scale (VAS), the Oswestry disability index (ODI), and the short form 36 (SF-36) were used to evaluate the clinical outcomes.

Results

The mean volume of the fusion-mass per level was 8,814 mm³, 8,035 mm³, 8,383 mm³, and 7,550 mm³ in groups 1, 2, 3, and 4, respectively, but there were no significant differences between the groups (p = 0.829). There were no significant decreases in the volume of the fusion-mass (p = 0.533) in the zoledronic acid groups (groups 1 and 2). The VAS, the ODI, and the SF-36 at the 6-month follow-up after surgery were not significantly different (p > 0.05) among the 4 groups. The VAS, the ODI, and the SF-36 were not correlated with the volume of the fusion-mass (p = 0.120, 0.609, 0.642).

Conclusions

A single dose of zoledronic acid does not decrease the volume of the fusion-mass in patients undergoing spinal fusion with osteoporosis. Therefore, we recommend that zoledronic acid may be used after spinal fusion in osteoporotic patients.     

Skeletal morbidity in men with prostate cancer: quality-of-life considerations throughout the continuum of care

OBJECTIVE: With current treatments, men usually survive many years after being diagnosed with prostate cancer. However, without supportive care, the systemic effects of prostate cancer and therapies such as androgen deprivation therapy (ADT) can undermine skeletal integrity, resulting in skeletal complications that may erode quality of life (QOL). Prostate cancer patients are at risk for fractures from cancer treatment-induced bone loss. In addition, they are also at risk for pathologic fractures, severe bone pain, and other sequelae from bone metastases, which almost invariably occur during the progression of prostate cancer. This review investigates the incidence and pathophysiology of bone loss and skeletal morbidity in prostate cancer patients and reviews available treatment options for maintaining skeletal health throughout the continuum of care for these patients. METHODS: Studies were identified through MEDLINE searches, review of bibliographies of relevant articles, and review of abstracts from national meetings. RESULTS: Several supportive care options are available to prevent generalized and localized bone loss, including calcium and vitamin D supplements and bisphosphonates. Oral calcium and vitamin D supplementation alone, however, appears to be insufficient to prevent bone loss during ADT. Zoledronic acid administered every 3 months during ADT or every 3 to 4 weeks for patients with bone metastases can reverse bone loss and reduce skeletal morbidity, respectively, in patients with prostate cancer. CONCLUSIONS: Skeletal complications contribute to the erosion of QOL in prostate cancer patients. Palliative care can provide important benefits to these patients. Some agents, such as zoledronic acid, may provide skeletal health benefits throughout the course of prostate cancer progression. Further investigations of the QOL impact of these benefits are warranted.     

唑来膦酸联合钙剂治疗老年慢性阻塞性肺疾病患者骨质疏松症的临床疗效

目的研究老年慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)合并骨质疏松症患者应用唑来膦酸结合钙尔奇对患者骨密度、生化与骨代谢相关指标的影响。方法 102例COPD合并骨质疏松症患者,按随机数字表法将其分为治疗组(n=51)及对照组(n=51)。对照组给予钙尔奇治疗,治疗组给予唑来膦酸联合钙尔奇治疗,为期12个月。检测治疗后两组患者的腰椎1~4(L1~4)、股骨颈骨密度及血钙(Ca)、血磷(P)、25羟基维生素D[25(OH)D3]、甲状旁腺素(parathyroid hormone,PTH)、骨钙素(osteocalcin,OC)、1型胶原羧基末端肽(type 1 collagen carboxy terminal peptide,β-CTX)、1型前胶原氨基端肽(type 1 procollagen amino terminal peptide,P1NP)、骨源性碱性磷酸酶(bone alkaline phosphatase,BALP)水平的变化情况,记录两组患者药物的不良反应。结果治疗后12个月后,治疗组腰椎1~4(L1~4)、股骨颈骨密度均显著高于同时期对照组(P0.05);治疗后6个月后,治疗组患者血清PTH、OC、P1NP、BALP均显著高于治疗前(P0.05),而25(OH)D3及β-CTX均显著低于治疗前(P0.05),而Ca、P差异无统计学意义(P0.05)。两组药品不良反应发生率比较,差异无统计学意义(P0.05)。结论唑来膦酸联合钙剂提升COPD患者骨密度,改善骨代谢状态,可以安全有效地防治老年COPD合并骨质疏松症。     

The Effect of Prior Bisphosphonate Exposure on the Treatment Response to Teriparatide in Clinical Practice

Our objective was to determine the effect of prior bisphosphonate exposure on the treatment response to teriparatide. All patients started on teriparatide in our hospital are entered into a database. All patients who had at least 12 months’ treatment were identified. Patients were divided into two groups depending on whether or not they had prior bisphosphonate exposure, and the response to teriparatide was compared using procollagen of type 1 N-terminal propeptide (P1NP) and bone mineral density (BMD). Fifty-two patients had been treated for at least 12 months, 38 with prior bisphosphonate exposure and 14 without. The mean duration of bisphosphonate treatment was 67 months, discontinued a mean of 1 month previously. P1NP increased significantly at 3 and 6 months in both groups. However, those without previous bisphosphonate treatment had a higher baseline P1NP (49 vs. 30 μg/L, P < 0.01), and this remained higher at 3 months (109 vs. 71 μg/L, P = 0.10) and 6 months (183 vs. 126 μg/L, P = 0.06), although the difference was not significant. In the prior bisphosphonate and bisphosphonate naive groups, respectively, the change in spinal BMD was 9.0% and 7.8% (P = 0.54) at 12 months and 9.8% and 6.1% (P = 0.30) at 18 months. The respective change in hip BMD was 1.0% and −0.3% (P = 0.36) at 12 months and 2.8% and 1.3% (P = 0.44) at 18 months. There was a trend toward a smaller but still significant increase in P1NP in response to teriparatide in bisphosphonate-treated patients. Although this suggests a blunting of the anabolic effects, in our clinic population this did not result in a reduction in BMD gain.     

Determination of rat vertebral bone compressive fatigue properties in untreated intact rats and zoledronic-acid-treated, ovariectomized rats

Summary  Compressive fatigue properties of whole vertebrae, which may be clinically relevant for osteoporotic vertebral fractures, were determined in untreated, intact rats and zoledronic-acid-treated, ovariectomized rats. Typical fatigue behavior was found and was similar to that seen in other species. Fatigue properties were comparable between both groups. Introduction  Osteoporosis is often treated with bisphosphonates, which reduce fracture risk. Effects of bisphosphonates on fatigue strength, which may be clinically relevant for vertebral fractures, are unknown. We determined vertebral, compressive fatigue properties in normal and zoledronic acid (ZOL)-treated, OVX rats. Methods  Thirty-five-week old Wistar rats were divided into SHAM-OVX (n = 7) and OVX with ZOL treatment (n = 5; single injection, 20 μg/kg b.w. s.c.). After 16 weeks, vertebral trabecular microarchitecture and cortical thickness were determined using micro-CT. Vertebrae were cyclically compressed in load-control at 2 Hz starting at 0.75% apparent strain. A line parallel to the apparent strain curve was drawn at 0.5% higher offset, after which the intersection was defined as the time to failure and the apparent strain at failure. Data were compared using Student’s t test. Results  Morphology and fatigue properties were the same in both groups. Samples failed between 10 min and 15 h. Force–displacement curves displayed typical fatigue behavior. Displacement increased over time due to mostly creep and to decreasing secant stiffness. Conclusions  We established a technique to determine compressive fatigue properties in the rat vertebral body. Our initial results indicate that ZOL-treated OVX rats have similar vertebral fatigue properties as SHAM-OVX controls.     

唑来膦酸、伊班膦酸钠及阿伦膦酸钠防治绝经后骨质疏松症的疗效对比研究

目的对比研究唑来膦酸、伊班膦酸钠及阿伦膦酸钠对绝经后骨质疏松症的疗效。方法 180名绝经后妇女随机分为唑来膦酸治疗组(ZOL组)、伊班膦酸钠治疗组(IBA组)和阿伦膦酸钠治疗组(ALN组);ZOL组给予唑来膦酸治疗,IBA组给予伊班膦酸钠治疗,ALN组予以阿伦膦酸钠治疗。治疗前后分别检测3组受试者腰椎及髋部骨密度、血清骨代谢指标、视觉模拟评分(visual analogue scale,VAS)改变及研究期间药物不良反应和骨折发生率。结果药物治疗12个月后3组腰椎(L1~4)及左侧股骨颈骨密度明显增加,显著高于治疗前(P0.05),而3组间比较差异无统计学意义(P0.05),3组治疗有效率比较差异无统计学意义(P0.05)。药物治疗12个月后3组患者的VAS评分均显著降低,显著低于治疗前(P0.05),而3组间比较差异无统计学意义(P0.05)。干预12个月后两组血清I型胶原交联羧基末端肽和抗酒石酸酸性磷酸酶-5b水平均显著降低,显著低于治疗前(P0.05),而3组间比较差异无统计学意义(P0.05)。3组间药物不良反应发生率比较差异无统计学意义(P0.05)。结论唑来膦酸、伊班膦酸钠及阿伦膦酸钠对绝经后骨质疏松症的治疗安全有效,可以显著改善骨密度及骨代谢异常。     

Cancer Pain Management and Bone Metastases: An Update for the Clinician

Breast cancer patients with bone metastases often suffer from cancer pain. In general, cancer pain treatment is far from being optimal for many patients. To date, morphine remains the gold standard as first-line therapy, but other pure μ agonists such as hydromorphone, fentanyl, or oxycodone can be considered. Transdermal opioids are an important option if the oral route is impossible. Due to its complex pharmacology, methadone should be restricted to patients with difficult pain syndromes. The availability of a fixed combination of oxycodone and naloxone is a promising development for the reduction of opioid induced constipation. Especially bone metastases often result in breakthrough pain episodes. Thus, the provision of an on-demand opioid (e.g., immediate-release morphine or rapid-onset fentanyl) in addition to the baseline (regular) opioid therapy (e.g., sustained-release morphine tablets) is mandatory. Recently, rapid onset fentanyls (buccal or nasal) have been strongly recommended for breakthrough cancer pain due to their fast onset and their shorter duration of action. If available, metamizole is an alternative non-steroid-anti-inflammatory-drug. The indication for bisphosphonates should always be checked early in the disease. In advanced cancer stages, glucocorticoids are an important treatment option. If bone metastases lead to neuropathic pain, coanalgetics (e.g., pregabalin) should be initiated. In localized bone pain, radiotherapy is the gold standard for pain reduction in addition to pharmacologic pain management. In diffuse bone pain radionuclids (such as samarium) can be beneficial. Invasive measures (e.g., neuroaxial blockage) are rarely necessary but are an important option if patients with cancer pain syndromes are refractory to pharmacologic management and radiotherapy as described above. Clinical guidelines agree that cancer pain management in incurable cancer is best provided as part of a multiprofessional palliative care approach and all other domains of suffering (psychosocial, spiritual, and existential) need to be carefully addressed («total pain»).     

Intermittent Oral Disodium Pamidronate in Established Osteoporosis: A 2 Year Double-Masked Placebo-Controlled Study of Efficacy and Safety

The effect of oral pamidronate on bone mineral density and its adverse effect profile was investigated by a double-masked placebo-controlled study of 122 patients aged 55–75 years with established vertebral osteoporosis. Patients on active therapy received disodium pamidronate 300 mg/day (group A) for 4 weeks every 16 weeks, 150 mg/day (group B) for 4 weeks every 8 weeks or placebo (group C). All patients additionally received 500 mg of calcium and 400 IU vitamin D daily. Dual-energy X-ray absorptiometry measurements of the spine, hip, forearm and total body were performed at baseline and 6-monthly for 2 years using a Hologic QDR 1000 device at two sites. Serum osteocalcin and urinary deoxypyridinoline were measured at the above visits and at 3 months. The percentage change (SEM) in spine bone mineral density (BMD) at 2 years based on intention-to-treat analysis was 4.64 (1.01) in group A, 6.10 (0.87) in group B and 1.13 (1.32) in group C. Analysis of variance showed significant increases in group A and B compared with placebo (p<0.01). There were also significant rises in femoral neck BMD for group A (p = 0.005), trochanter BMD for groups A and B (p<0.01) and total-body BMD for groups A and B (p<0.001). There was a significant reduction in serum osteocalcin and urinary deoxypyridinoline for groups A and B (p<0.01). There was an excess of gastrointestinal side-effects in the treated groups, particularly group A. We conclude that intermittent pamidronate therapy can prevent bone loss at both the lumbar spine and femoral neck in patients with established vertebral osteoporosis, although due to gastrointestinal side-effects the 300 mg dose in particular does not appear suitable for clinical usage. Received: 12 January 1999 / Accepted: 30 August 1999     

Clinical Guidelines in the Management of Frozen Shoulder: An Update!

Among all the prevalent painful conditions of the shoulder, frozen shoulder remains one of the most debated and ill-understood conditions. It is a condition often associated with diabetes and thyroid dysfunction, and which should always be investigated in patients with a primary stiff shoulder. Though the duration of ‘traditional clinicopathological staging’ of frozen shoulder is not constant and varies with the intervention(s), the classification certainly helps the clinician in planning the treatment of frozen shoulder at various stages. Most patients respond very well to combination of conservative treatment resulting in gradual resolution of symptoms in 12–18 months. However, the most effective treatment in isolation is uncertain. Currently, resistant cases that do not respond to conservative treatment for 6–9 months could be offered surgical treatment as either arthroscopic capsular release or manipulation under anaesthesia. Though both invasive options are not clinically superior to another, but manipulation could result in unwarranted complications like fractures of humerus or rotator cuff tear.     

Influence of Factors Regulating Bone Formation and Remodeling on Bone Quality in Osteonecrosis of the Femoral Head

Osteonecrosis of the femoral head (ONFH) usually affects young individuals and has a major impact on lifestyle. Notably, the pathogenetic mechanisms of osteonecrosis are unresolved and no effective treatment exists. The objective of this study was to assess the gene expression levels of factors regulating bone formation and remodeling (bone morphogenetic protein [BMP]-2, BMP-7, Runx2, osteocalcin, osteoprotegerin [OPG]) in patients with ONFH and to compare them to those of patients with primary osteoarthritis (OA). The cellular and macromolecular composition of the bone matrix was assessed by osteocalcin immunohistochemistry, and the three-dimensional organization of trabecular bone was characterized by micro-computed tomographic analysis. Our results demonstrate that gene expression of BMP-2, BMP-7, and Runx2 is elevated in patients with ONFH. We observed increased extracellular osteocalcin deposition, presumably caused by a higher number of osteoblasts in concordance with increased activity of Runx2. Constant gene expression level of OPG implies an unchanged osteoclast differentiation rate in ONFH bone. We found no significant change in bone volume, connectivity, and structural model index; further, no significant differences were detected for trabecular properties in ONFH bone. In conclusion, we have shown increased gene expression of factors regulating bone formation and remodeling in the femoral head and/or neck of patients with ONFH. Further, we observed an increase in osteocalcin immunoreactivity and osteoblast/osteocyte cell number, while no significant changes in trabecular microarchitecture were detected. This study increases our understanding of the pathophysiology and repair process following ONFH and might help in the development of new treatment strategies in the future.     

Management of cancer treatment-induced bone loss in early breast and prostate cancer - a consensus paper of the Belgian Bone Club

Cancer treatment-induced bone loss (CTIBL) is one of the most important side effects of adjuvant antineoplastic treatment in hormone-dependent neoplasms. Chemotherapy, GnRH analogs and tamoxifen can induce marked bone loss in premenopausal women with early breast cancer. Aromatase inhibitors (AIs) are replacing tamoxifen as the preferred treatment for postmenopausal women. As a class effect, steroidal (exemestane) and non-steroidal (anastrozole and letrozole) AIs increase bone turnover and cause bone loss (4%-5% over 2 years). When compared to tamoxifen, the risk of getting a clinical fracture under AI treatment is increased by 35%-50%. In patients with prostate cancer, androgen deprivation therapy (ADT) increases bone turnover, reduces bone mass (4%-5% per year) and increases the fracture rate depending on the duration of therapy. Zoledronic acid can prevent accelerated bone loss induced by goserelin in premenopausal women, by letrozole in postmenopausal women and by ADT in men. More limited data indicate that weekly alendronate or risedronate could also be effective for preventing CTIBL. Initiation of therapy early, prior to the occurrence of severe osteoporosis, rather than after, may be more effective. Bisphosphonate treatment should be considered in osteoporotic but also in osteopenic patients if other risk factor(s) for fractures are present.     

The effects of hydrocortisone,parathyroid hormone and the bisphosphonate,APD, on bone resorption in neonatal mouse calvaria

Summary The effects of hydrocortisone and parathyroid hormone (PTH) upon bone resorption rates in neonatal mouse calvaria have been studied. Bone resorption (measured as⁴⁵Ca release) was significantly increased by hydrocortisone (10⁻⁷ M and 10⁻⁶ M) and there was a dose-dependent rise with PTH (0.3–0.9 μg/liter). When both PTH 0.3 μg/liter and hydrocortisone 10⁻⁸ M were present in the incubating medium, bone resorption did not differ from control, but increasing the hydrocortisone concentration to 10⁻⁷ M augmented⁴⁵Ca release by 25% (P<0.02) and doubling of the PTH level was associated with a 10% increase (nonsignificant). When both PTH and hydrocortisone were present in the higher concentrations (0.6 μg/liter and 10⁻⁷ M, respectively)⁴⁵Ca release increased by 39% (P<0.005) above that resulting from the lower levels of both hormones (0.3 μg/l and 10⁻⁸ M, respectively). (3-Amino-1-hydroxypropylidene)-1,1-bisphosphonate (APD) in concentrations of 3×10⁻⁵ M and 10⁻⁴ M, produced inhibition of basal and hydrocortisone/PTH-stimulated bone resorption without evidence of toxicity. These results indicate that hydrocortisone stimulates bone resorption in neonatal mouse calvariain vitro, in contrast to the result found in fetal rat bone culture systems. PTH has a similar effect, which is additive to that of hydrocortisone and the combined stimulation can be overcome by APD. The possible relevance of these results to the development and prevention of glucocorticoid-induced osteoporosis is discussed.     

高龄老年骨质疏松症患者应用唑来膦酸注射液的安全性及疗效初步分析

目的 观察唑来膦酸注射液（密固达）治疗80岁以上高龄老年骨质疏松症患者的安全性,并进行疗效分析。方法 将肌酐清除率≥30mL/min且伴明显骨痛症状的60例高龄老年骨质疏松症患者随机分成研究组和对照组,每组各30例。研究组采用密固达联合钙剂和维生素D治疗,对照组单纯使用钙剂和维生素D治疗。治疗前和治疗12个月后分别进行疼痛评分、生活质量测评及骨密度测定。结果 研究组应用密固达后肾功能无明显损害,无严重毒副反应发生,疼痛评分变化达显效和有效标准的分别为16例和10例,疼痛缓解总有效率为86.7%;而对照组达到相应标准的分别为1例和3例,总有效率为13.3%。治疗后研究组患者的生活质量得到显著改善;且腰椎（L2-4)、右股骨颈及右侧全髋的骨密度较治疗前显著增加;上述指标与对照组相比均有显著差异(P<0.01)。结论 密固达治疗高龄老年骨质疏松症有较高的安全性和较好的疗效。