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.     

Treatment of bisphosphonate-related osteonecrosis of the jaws: presentation of a protocol and an observational longitudinal study of an Italian series of cases

The aim of this study was to evaluate the efficacy of a treatment protocol for bisphosphonate-related osteonecrosis of the jaws (BRONJs). We conducted a longitudinal observational non-controlled study in 94 patients with confirmed BRONJ. Treatment was in two phases: supportive (antimicrobial mouth rinses, antibiotics, and anti-inflammatory steroids) to minimise infection and pain before the formation of a bony sequestrum; and surgical plus pharmacological treatment (sequestrectomy with antibiotic prophylaxis) after the sequestrum had developed. We did a Kaplan-Meier analysis (survival curve) to evaluate the time from the initial assessment until the formation of the bony sequestrum (endpoint), and a log-rank (Mantel-Haenszel) test to compare the formation times of the sequestra in men and women. Ninety-one of the 94 patients developed sequestra and were operated on. Three patients were withdrawn from the study because of severe pain and were treated by debridement before the sequestra developed. The results showed that sequestra developed within 15 months in all 91 patients. The Kaplan-Meier analysis showed that the mean time to formation of a sequestrum was 8 months (range 5-11). The difference between the mean time for men (5 months, range 2-8) and women (9 months, range 6-12) was highly significant (p<0.0001). Within the limits of this study, we conclude that by waiting for the formation of bony sequestra while controlling infection and pain, it is possible to do a conservative resection, unless pain is severe or there is a risk of fracture. This non-aggressive approach permits the removal of all necrotic bone, avoids damage to adjacent healthy bone, and does not result in recurrences.     

The use of bisphosphonates in children: review of the literature and guidelines for dental management

Bisphosphonates are inhibitors of osteoclastic bone resorption with therapeutic benefit in a variety of bone disorders in both adults and children. While these agents have been routinely used in adults for the past three decades, their more recent introduction into paediatric medicine means there is a paucity of data on long‐term safety and effects on dental development. There is uncertainty regarding the dental management of children treated with bisphosphonates, particularly when invasive dental procedures, such as extractions and oral surgical procedures, are required. There are limited data with which to make recommendations about the dental management of patients treated with bisphosphonates, and there are no published recommendations that specifically address paediatric patients. This paper aims to outline paediatric uses and adverse effects of bisphosphonates and present recommendations on the dental management of children receiving bisphosphonates.     

Staging of osteonecrosis of the jaw requires computed tomography for accurate definition of the extent of bony disease

Management of osteonecrosis of the jaw associated with antiresorptive agents is challenging, and outcomes are unpredictable. The severity of disease is the main guide to management, and can help to predict prognosis. Most available staging systems for osteonecrosis, including the widely-used American Association of Oral and Maxillofacial Surgeons (AAOMS) system, classify severity on the basis of clinical and radiographic findings. However, clinical inspection and radiography are limited in their ability to identify the extent of necrotic bone disease compared with computed tomography (CT). We have organised a large multicentre retrospective study (known as MISSION) to investigate the agreement between the AAOMS staging system and the extent of osteonecrosis of the jaw (focal compared with diffuse involvement of bone) as detected on CT. We studied 799 patients with detailed clinical phenotyping who had CT images taken. Features of diffuse bone disease were identified on CT within all AAOMS stages (20%, 8%, 48%, and 24% of patients in stages 0, 1, 2, and 3, respectively). Of the patients classified as stage 0, 110/192 (57%) had diffuse disease on CT, and about 1 in 3 with CT evidence of diffuse bone disease was misclassified by the AAOMS system as having stages 0 and 1 osteonecrosis. In addition, more than a third of patients with AAOMS stage 2 (142/405, 35%) had focal bone disease on CT. We conclude that the AAOMS staging system does not correctly identify the extent of bony disease in patients with osteonecrosis of the jaw.     

Leucocyte-rich and platelet-rich fibrin for the treatment of bisphosphonate-related osteonecrosis of the jaw: a prospective feasibility study

Our aim was to assess the feasibility of using leucocyte-rich and platelet-rich fibrin (L-PRF) for the treatment of bisphosphonate-related osteonecrosis of the jaw (BRONJ) in a single group study. After treatment with L-PRF, the response of each patient was recorded 1 month and 4 months postoperatively. Further assessments were made of the site, stage, concentration of c-terminal crosslinked telopepide of type 1 collagen, and actinomycosis. Among the total of 34 patients, 26 (77%) showed complete resolution, 6 (18%) had delayed resolution, and 2 (6%) showed no resolution. There was a significant association between the response to treatment and the stage of BRONJ (p = 0.002) but no other significant associations were detected. This study has shown that it is feasible to use L-PRF for the treatment of BRONJ, but the effectiveness cannot be judged with this study design. Randomised prospective trials are needed to confirm this.     

Bisphosphonate Related Osteonecrosis of the Jaw: An Update

Objectives

The aim of this paper is to summarize different diagnostic criteria as well as probable aetiopathogenesis of bisphosphonates related osteonecrosis of the jaw.

Materials and Methods

The electronic search of peer-reviewed journals were performed in MEDLINE (PubMed) database in order to find the relevant articles on bisphosphonates related osteonecrosis of the jaw (BP-related ONJ). The search was restricted to English language articles, published from January 2002 to May 2013. On the basis of these articles, probable aetiopathogenesis and different diagnostic criteria of BP-related ONJ were summarized.

Results

BP-related ONJ is related to the development of avascular necrosis or dead jaw bones. In recent literature many given hypotheses show the aetiopathogenesis and diagnosis of BP-related ONJ which are interlinked and have multifactorial nature. Their diagnosis revolves around four main diagnostic criteria that differentiate it from other conditions which can delay bone healing.

Conclusions

Factors like potency of bisphosphonates, biology of jaw bone, antiangiogenic property of bisphosphonates and soft tissue toxicity in combination with present infection, other drugs, pre-existing pathologies, compromised immune response and dentoalveolar trauma may lead to development of BP-related ONJ.     

Potential significance of antiestrogen therapy in the development of bisphosphonate related osteonecrosis of the jaw

ObjectivesThere are known risk factors and established treatment protocols for bisphosphonate-related osteonecrosis of the jaw (BRONJ), but it remains a difficult disease to treat, with the risk of relapses. This study investigates whether or not there is a relationship between antiestrogen therapy and BRONJ.Patients and methodsIn our prospective study, we followed up 93 patients with BRONJ who were seen at our clinic between 2006 and 2011.ResultsWe found that breast cancer patients had a significantly worse prognosis than patients with other underlying illnesses (p < 0.01), which might indicate the role of antiestrogen therapy (p < 0.001) as a causative factor.ConclusionThe dominance of the female gender among BRONJ patients as well as our new findings related to antiestrogen therapy of breast cancer raise the possibility that estrogen deficiency might be a newly discovered risk factor for BRONJ.     

Biochemical bone markers in the assessment and pamidronate treatment of children and adolescents with osteogenesis imperfecta

Aim: To assess the role of biochemical bone markers in classification of children with osteogenesis imperfecta (OI), their possible association with vertebral compression fractures in milder forms of OI and their role in monitoring of intravenous pamidronate (APD) treatment. Methods: Serum total alkaline phosphatase (ALP), bone ALP isoforms (in a subgroup), osteocalcin, type I procollagen carboxy‐terminal propeptide, carboxy‐terminal telopeptide of type I collagen, and urine deoxypyridinoline (DPD) were measured in a cross‐sectional study of 130 untreated individuals, 0.25–20.9 years (median 6.7), with OI types I, III and IV. Of those, sixty‐nine were also assessed longitudinally during monthly APD treatment. Bone mineral density (BMD) was measured by dual‐energy X‐ray absorptiometry. Results: Significant differences in bone markers, however not sufficient for individual clinical use, were found in the larger untreated group but not between subgroups with or without vertebral compressions. All bone markers decreased during treatment for 1.0–12.5 years, but with different relative amounts. Changes were not correlated to the improvement in BMD, mobility or pain. Conclusion: Bone markers are, despite significant differences, not useful for the classification of OI type in the individual child and are not associated with vertebral compressions. Serum ALP and urinary DPD are sensitive in monitoring bisphosphonate treatment.