The Spine Journal 12 (2012) 304–312
Clinical Study
Hypovitaminosis D as a risk factor of subsequent vertebral fractures after kyphoplasty Christos P. Zafeiris, MSc, MDa,b,c,*, George P. Lyritis, MD, PhDa,b, Nikolaos A. Papaioannou, MD, PhDa,b, Peter E. Gratsias, MDc, Antonios Galanos, BSc, PhDa, Sofia N. Chatziioannou, MD, PhDd, Spyros G. Pneumaticos, MD, PhDc a
Laboratory for the Research of the Musculoskeletal System (LRMS), Postgraduate Course on Metabolic Bone Disease, Faculty of Medicine, University of Athens, 2nd Nikis St, Kifisia 145 61, Athens, Greece b Hellenic Osteoporosis Foundation, 5th Agias Varvaras St, Kifisia 145 61, Athens, Greece c Third Department of Orthopaedic Surgery, Faculty of Medicine, University of Athens, ‘‘KAT’’ Accident’s Hospital, Athens, Greece d Department of Radiology, Faculty of Medicine, University of Athens, ‘‘Attikon’’ General Hospital, 1st Rimini St, Chaidari 124 62, Athens, Greece Received 14 April 2011; revised 30 November 2011; accepted 14 February 2012
Abstract
BACKGROUND CONTEXT: Over the past 20 years, methods of minimally invasive surgery have been developed for the treatment of vertebral compression fractures. Balloon kyphoplasty and vertebroplasty are associated with a recurrent fracture risk in the adjacent levels after the surgical procedure. In certain patient categories with impaired bone metabolism, the risk of subsequent fractures after kyphoplasty is increased. PURPOSE: To determine the incidence of recurrent fractures after kyphoplasty and explore whether the status of bone metabolism and 25-hydroxyvitamin D (25(OH)D) levels affect the occurrence of these fractures. STUDY DESIGN: Prospective longitudinal clinical study. PATIENT SAMPLE: Forty female postmenopausal women with primary osteoporosis and acute symptomatic vertebral compression fractures. OUTCOME MEASURES: Identification of new vertebral fractures and documentation of indicators of bone metabolism. METHODS: A total of ninety-eight kyphoplasties were performed in 40 female patients. Balloon kyphoplasty was performed on all symptomatic acute vertebral compression fractures. Age, body mass index, history of tobacco use, number of initial vertebral fractures, intradiscal cement leakage, history of nonspinal fractures, use of antiosteoporotic medications, bone mineral density, bone turnover markers, and 25(OH)D levels were assessed. All participants were evaluated clinically and/or radiographically. Follow-up period was 18 months. RESULTS: The mean population age was 70.6 years (range, 40–83 years). After initial kyphoplasty procedure, nine patients (11 levels) (22.5% of patients; 11.2% of levels) developed a postkyphoplasty vertebral compression fracture. Cement leakage was identified in seven patients (17.5%). The patients without recurrent fractures after kyphoplasty demonstrated higher levels of 25(OH)D (22.665.51 vs. 14.3967.47; p5.001) and lower N-terminal cross-linked telopeptide values (17.11610.20 vs. 12.9064.05; p5.067) compared with the patients with recurrent fractures. CONCLUSIONS: Bone metabolism and 25(OH)D levels seem to play a role in the occurrence of postkyphoplasty recurrent vertebral compression fractures. Ó 2012 Elsevier Inc. All rights reserved.
Keywords:
Kyphoplasty; Osteoporosis; Recurrent fractures; Bone metabolism; Hypovitaminosis D
FDA device/drug status: Not applicable. Author disclosures: CPZ: Nothing to disclose. GPL: Nothing to disclose. NAP: Nothing to disclose. PEG: Nothing to disclose. AG: Nothing to disclose. SNC: Nothing to disclose. SGP: Nothing to disclose. 1529-9430/$ - see front matter Ó 2012 Elsevier Inc. All rights reserved. doi:10.1016/j.spinee.2012.02.016
* Corresponding author. ‘‘KAT’’ Accident’s Hospital, University of Athens, 2nd Nikis St, Kifisia 145 61, Athens, Greece. Tel.: (0030) 6978267115; (0030) 210-8018123; fax: (0030) 210-8018122. E-mail address:
[email protected] (C.P. Zafeiris)
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Introduction Vertebral compression fractures are among the most common complications of osteoporosis with significant socioeconomic consequences. An estimated 750,000 new vertebral fractures occur in the United States every year [1], whereas the burden of health management exceeds $700 million [2]. The vertebral fractures affect the patient’s overall health because of the direct and indirect effects on quality of life with increased morbidity and mortality [3–11]. Pain associated with vertebral fractures limits mobility of the patients and subsequently leads to depression and loss of selfindependence [12–14]. The presence of one or more vertebral fractures increases the risk of a new vertebral fracture by five-fold, although the incidence of a new vertebral fracture in the following year is approximately 20% [15,16]. Despite medical approach [17], as many as one-third of patients with vertebral fractures continue to experience severe pain that can lead to further disability [18] that requires long-term care and hospitalization. Over the past 20 years, methods of minimally invasive surgery have been developed, including vertebroplasty and kyphoplasty. The technique of vertebroplasty consists of fluoroscopically guided percutaneous insertion of a needle into the fractured vertebra and injection of polymethylmethacrylate cement. Kyphoplasty differs from vertebroplasty in that it involves the insertion of a balloon tamp [19]. The balloon tamp intends to reduce the deformity, to restore the vertebral body height while creating a cavity to be filled with polymethylmethacrylate. The complications of these techniques are bleeding, transitory increase in pain, cement leakage, spinal infection, rib fractures, symptomatic or asymptomatic pulmonary embolism, radiculopathy, and spinal cord compression from the extravagation of the cement. Balloon kyphoplasty and vertebroplasty are also associated with a recurrent fracture risk in the adjacent levels within a short period of time after the surgical procedure [19]. In recent years, there has been increasing interest regarding the incidence of recurrent vertebral fractures after each type of procedure and possible reasons for their occurrence. A number of variables, such as the number of levels treated, the age, the gender, the cement leakage, the role of intervertebral disc, the unipedicular or bipedicular kyphoplasty, the sagittal alignment, the amount or the type of cement injected, the bone mineral density measurements, and several other factors [20–29], have been evaluated by several studies in the development of the recurrent fractures and in the overall clinical outcome. At the present time, there are little and insufficient data concerning the evaluation of the metabolic profile of the patients who undergo kyphoplasty [30]. The present study was undertaken to evaluate the incidence of recurrent fractures after kyphoplasty and identify any association between these fractures and the metabolic risk factors.
Context Adjacent level fractures following vertebrolasty and kyphoplasty are common and can be problematic. In this study, the authors explore possible risk factors. Contribution In this relatively small prospective study that examined several potential risk factors for adjacent level fractures, only Hypovitaminosis D and cement leakage from the prior kyphoplasty were found to be risk factors. Implication The findings suggest that both technical and metabolic factors present risk. Importantly, both are somewhat controllable, either by vitamin supplementation or by technique modification. —The Editors
Methods A total of 98 kyphoplasties were performed in 40 women with an average age of 70.568.5 years, with acute symptomatic vertebral compression fractures with stable or deteriorative pain for up to 12 weeks (Fig. 1). Patients with multiple myeloma, primary or metastatic malignancies, rheumatic diseases or corticosteroid use, liver or kidney disease, or transplantation were excluded from the study (Table 1). A full medical history and physical examination at baseline were obtained. Body weight and height were obtained, and the body mass index was calculated. Patient’s medications, fracture history, family history of osteoporosis, number of pregnancies, smoking, alcohol consumption, and age of menarche and menopause were recorded. All patients underwent plain radiographs, magnetic resonance imaging (MRI), and bone scintigraphy. The criteria for diagnosis of vertebral fracture were deformation of the vertebral body according to Genant’s grading system on plain radiographs, replacement of bone marrow with edema at the same level (T1-weighted and T2-weighted series with fat saturation) on MRI, and horizontally increased tracer uptake in a vertebral body on bone scintigraphy. If there was a discordance between the findings on MRI and bone scintigraphy, the patient was excluded from the study. Bone mineral density was measured at the lumbar spine and femoral neck by using dual energy X-ray absorptiometry. Kyphoplasty was performed through standard bilateral transpedicular approach under general anesthesia. After surgery, biochemical analysis of bone turnover markers was performed for all the patients, to determine their bone metabolic profile and initiate or modify medical treatment, as needed.
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Fig. 1. Initial assessment of the patients, inclusion, and follow-up. MRI, magnetic resonance imaging.
Table 1 Inclusion and exclusion criteria Inclusion criteria
Exclusion criteria
Primary osteoporosis Acute osteoporotic vertebral compression fracture with vertebral body signal change on MRI Positive bone scintigraphy at symptomatic level/s Duration of fracture symptoms less than 12 weeks Ability to tolerate kyphoplasty procedure Written informed consent
Secondary osteoporosis Chronic osteoporotic vertebral compression fracture without vertebral body signal change on MRI Negative bone scintigraphy Discordance between the levels found on MRI and bone scintigraphy Duration of fracture symptoms more than 3 months Use of corticosteroids History of malignancy History of liver or kidney disease or transplantation Spinal tumor or infection Previous kyphoplasty/vertebroplasty Destruction of the posterior wall of the vertebral body Noncompliance Bony fragments on the spinal cord or neurologic complications
MRI, magnetic resonance imaging.
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Table 2 Demographic characteristics
Age Menarche Menopause Years since menopause Weight Height BMI Number of vertebral fractures before kyphoplasty
Group
N
Mean
SD
p Value
No subsequent fracture Subsequent fracture No subsequent fracture Subsequent fracture No subsequent fracture Subsequent fracture No subsequent fracture Subsequent fracture No subsequent fracture Subsequent fracture No subsequent fracture Subsequent fracture No subsequent fracture Subsequent fracture No subsequent fracture Subsequent fracture
31 9 31 9 31 9 31 9 31 9 31 9 31 9 31 9
70.42 71.00 12.90 12.56 45.58 48.78 24.84 22.22 66.16 63.89 154.61 149.89 27.66 28.33 2.35 2.78
9.01 6.96 1.22 1.51 4.99 4.15 8.86 8.33 10.51 13.29 7.38 5.62 3.82 4.81 1.20 1.30
.860 .480 .108 .435 .594 .185 .665 .366
SD, standard deviation; BMI, body mass index.
Biochemical analysis included serum total calcium and serum inorganic phosphate, which were measured by colorimetry using a Roche Hitachi 902 analyzer (Roche, Indianapolis, IN, USA). The intra- and interassay coefficients of variation (CVs) for calcium and phosphate determinations were 0.9 and 1.5% and 0.9 and 1.4%, respectively. Plasma intact parathyroid hormone was measured by an electrochemiluminescence immunoassay (Roche). The sensitivity was 1.2 pg/mL and the intra- and interassay CVs were 4 and 4.3%, respectively. Serum 25-hydroxyvitamin D (25(OH)D) was determined by enzyme immunoassay (OCTEIA; Immunodiagnostic Systems, Ltd., Boldon, Tyne and Wear, UK). The sensitivity was 5 nmol/L and the intra- and interassay CVs were 5.3 and 4.6%, respectively. Serum procollagen Type 1 N-propeptide was measured by electrochemiluminescence immunoassay (Roche). The sensitivity was 5 g/L and the intra- and interassay CVs were 2.2 and 2.9%, respectively. N-terminal cross-linked telopeptide (NTx) of Type 1 collagen was measured with a competitive inhibition enzyme-linked immunoassay (OSTEOMARK NTx Serum; Wampole Laboratories, Cranbury, NJ, USA), and the results were reported as nanomole bone collagen equivalents. In our institute, the intra- and interassay CVs were 4.6% and 6.9%, respectively. All participants were evaluated clinically and/or radiographically at 1 week and at 1, 3, 6, 12, and 18 months after the procedure. The patients were divided into two groups: the patients who developed a recurrent fracture after kyphoplasty, who will be referred to as the ‘‘fracture group,’’ and the patients who did not develop a postkyphoplasty vertebral fracture, who will be referred to as the ‘‘no fracture group.’’ The study was approved by the human research ethics committee of our institution. All procedures were performed at a single institution by the senior author. All patients received detailed explanation of the kyphoplasty procedure and the handling of clinical data. Written informed consent was obtained from each patient.
Statistical analysis Quantitative variables were expressed as the mean and standard deviation, whereas qualitative variables were given as frequencies and their corresponding percentages. Univariate analyses were made using the chi-square test or alternatively the Fisher exact test to analyze the relationship between the outcome variable and the qualitative variables. Student t test was used to analyze the relationship between the outcome variable and the quantitative measures, respectively. Two analyses were conducted. All factors that presented significant associations with outcome variable in univariate analysis were included in the final model using the enter Table 3 Demographic characteristics Subsequent fracture No
Yes
p Value
Complications (cement leakage) No n 27 % 81.8 Yes n 4 % 57.1
6 18.2 3 42.9
.316
Nonspinal fractures No n % Yes n %
22 81.5 9 69.2
5 18.5 4 30.8
.437
Use of antiosteoporotic medication No n 7 % 53.8 Yes n 24 % 88.9
6 46.2 3 11.1
.038
7 21.9 2 25.0
1.000
Smoking No Yes
n % n %
25 78.1 6 75.0
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Fig. 2. Distribution of the initial and the subsequent fracture levels.
method. All potential risk factors, whether they demonstrated significant associations with outcome variable in univariate analysis, were included in the model. Stepwise elimination (Wald method) was used to reach the final model. Goodness of fit was evaluated using the Hosmer-Lemeshow statistic. A p value less than .05 (two sided) was used to denote statistical significance, although associations reaching borderline significance (.05!p!.1) were also identified as being of potential interest. All analyses were carried out using the statistical package SPSS version 16.00 (SPSS, Inc., Chicago, IL, USA).
kyphoplasty at 98 vertebral levels between T6 and L5 (Figs. 1 and 2). The most commonly treated vertebrae were T12, T11, and L1 with 19, 17, and 16 fractures, respectively. Nine patients (22.5% of patients) developed a new vertebral compression fracture at an adjacent level. Fig. 2 shows the fracture distribution at each level of the spinal column. Looking at the number of levels treated (98 levels), new fractures occurred in 11 (11.2% of levels). Demographic characteristics are summarized in Tables 2 and 3. Age, body mass index, history of tobacco use, number of initial vertebral fractures, complications of the technique (cement leakage), history of nonspinal fractures, use of antiosteoporotic medications were not found to correlate with the risk of recurrent fracture (pO.05; Tables 2 and 3). The majority of the patients were receiving oral bisphosphonates and Ca/vitamin D supplements, with the exception of few who were receiving teriparatide or strontium ranelate (and Ca/vitamin D supplements). The nine patients with recurrent fractures had 11 involved vertebrae: nine were adjacent to the kyphoplasty level, whereas the remaining two occurred in a remote vertebra (a remote level is defined as a level with at least one unaffected level between the initially treated fracture and the subsequent one). Cement leakage in the intervertebral disc was identified as an adverse event in 17.5% (n57) of overall treated patients, whereas the percentage per group was 12.9% (n54) and 33.3% (n53) for the group without fracture postoperatively and the group with recurrent fractures, respectively (p5not significant). History of nonspinal fractures, use of antiosteoporotic medication, and smoking were not found to demonstrate a statistical correlation with the final outcome of the procedure (Table 3). The laboratory evaluation of the patients showed that there was no statistically significant difference in total serum calcium, serum inorganic phosphate, intact parathyroid hormone, procollagen Type 1 N-propeptide, and creatinine Table 4 Laboratory findings of all subjects
Ca P PTH 25(OH)D NTx P1NP
Results The main characteristics of the entire study population are shown in Tables 1–3. The mean population age was 70.6 years (range, 40–83 years). The follow-up period was 18 months for all patients. Forty patients underwent
Creatinine
Group
n
Mean
SD
p Value
No fracture Fracture No fracture Fracture No fracture Fracture No fracture Fracture No fracture Fracture No fracture Fracture No fracture Fracture
31 9 31 9 31 9 31 9 31 9 31 9 31 9
9.46 9.81 3.49 3.79 50.68 46.16 22.60 14.39 12.90 17.11 43.19 54.53 0.88 0.81
0.61 0.67 0.58 0.64 28.26 15.38 5.51 7.47 4.05 10.20 36.70 31.83 0.24 0.11
.148 .193 .650 .001 .067 .407 .383
SD, standard deviation; Ca, calcium; P, phosphorus; PTH, parathyroid hormone; 25(OH)D, 25-hydroxyvitamin D; NTx, N-terminal cross-linked telopeptide; P1NP, procollagen Type 1 N-propeptide.
C.P. Zafeiris et al. / The Spine Journal 12 (2012) 304–312 Table 5 Bone mineral density parameters in individuals without fractures and with subsequent fractures after kyphoplasty Group
n
Mean (g/cm2)
SD
p Value
BMD wards
No fracture No fracture
BMD total
No fracture
BMD neck
No fracture
BMD L2–L4
No fracture
0.51 0.48 0.62 0.58 0.73 0.69 0.68 0.64 0.82 0.80
0.07 0.08 0.09 0.05 0.07 0.06 0.06 0.08 0.11 0.12
.366
BMD trochanter
31 9 31 9 31 9 31 9 31 9
.204 .105 .100 .681
SD, standard deviation; BMD, bone mineral density.
levels between the fracture and no fracture group (Table 4). Statistically significant difference between the two groups was observed in serum levels for 25(OH)D. It was observed that the no fracture group had higher levels of 25(OH)D compared with the fracture group (22.665.51 vs. 14.3967.47; p5.001). Also, higher NTx values, with a statistical trend, were observed in the fracture group in relation with the no fracture group (17.11610.20 vs. 12.9064.05; p5.067) (Table 4). There was no statistical difference in bone mineral density measurements in all evaluated sites (lumbar spine, femoral neck, wards, trochanter, and total femur between the two groups [Table 5]). According to our multivariate analysis (stepwise, Wald) (Table 6), the only factors with statistical significance concerning the recurrent fractures were cement leakage and 25(OH)D levels. Our findings demonstrate that an increase by one unit reduces the fracture probability by 26%, whereas the cement leakage as a complication was a significant predictor of new vertebral body fracture by 7.96 times (95% confidence interval, 0.74–85.80). It was calculated that a sample size of 31 and nine patients per group achieved 86% power to detect a difference of 8.2 (22.6 vs. 14.4; standard deviation, 6) in 25(OH)D with a significance of less than 5% (two-tailed test). Discussion Kyphoplasty is a relatively recent technique with remarkable results in managing pain of osteoporotic vertebral Table 6 Multivariate analysis—all variables, stepwise, Wald analysis Reference category Complication (cement leakage) 25(OH)D Constant
No
Odds ratio
95% CI LL
95% CI UL
p Value
7.96
0.74
85.80
.087
0.74 134.56
0.59
0.92
.008 .027
CI, confidence interval; LL, log likelihood; UL, upper limit; 25(OH)D, 25-hydroxyvitamin D; LCS, likelihood chi-square; df, degrees of freedom. 2 LL527.63, LCS515.02, df52, and p5.001.
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fractures [31–37]. However, there are studies questioning its effectiveness overtime in pain recession, as well as its potential impact of the biomechanical alterations in the aging spine [38]. However, there is strong evidence that kyphoplasty has a beneficial effect on the immediate pain relief in early postoperative period. The possible occurrence of recurrent fractures after the procedure has major clinical importance and affects significantly the quality of the patient’s life. The incidence of recurrent fractures in the present study was 22.5%. Our findings are in agreement with the reported incidence in current literature. Available published data describe a 3% to 29% rate of recurrent fractures after kyphoplasty and 12% to 52% after vertebroplasty [39]. Several hypotheses are expressed for the mechanism of the occurrence of recurrent fractures after kyphoplasty or vertebroplasty. Some argue [40,41] that recurrent fractures result because of the increased activity of the patients because of pain relief and return to full social life after the surgical procedure. Others support [16,39] the natural progression of osteoporosis as responsible for the recurrent fractures, even without kyphoplasty or vertebroplasty. Lindsay et al. found that in the first year after sustaining an initial fracture, the risk of sustaining a recurrent fracture is as high as 19.2%. The risk for patients with greater than one initial vertebral fracture is 24%. Finally, it has been hypothesized that the biomechanical alterations that are induced by the technique may result in recurrent fractures [20,42,43]. The cement increases the stiffness in the treated vertebrae and thereby produces increased loading in the adjacent vertebrae. We believe that these fractures occur as a result of the combination of these mechanisms of the altered biomechanics associated with the suboptimal levels of bone metabolism. Bone metabolism seems to play a key role in the success of the technique. Osteoporosis is a disease that leads not only to a quantitative reduction of bone tissue but also to a disruption of the quality characteristics that affect the final outcome of kyphoplasty or vertebroplasty. It has been previously reported that in certain patient categories with impaired bone metabolism, such as patients under corticosteroid treatment or transplant recipients, the risk of recurrent fractures after kyphoplasty is increased [44,45]. Bone remodeling is a continuous rebuilding of the bone tissue through a coordinated process of bone resorption and subsequent bone formation in the basic multicellular units, by interacting actions of osteoblasts and osteoclasts. An increased rate of bone remodeling, which is common in many metabolic bone diseases such as osteomalacia, leads to an accelerated bone loss and increased risk of fracture. High bone turnover causes a deterioration of bone tissue and decreased rate of newly mineralized bone, with reduced mechanical strength and biomechanical properties [46]. Vitamin D deficiency and/or osteomalacia [47,48] creates an unstable, biomechanically weak bone microenvironment as a result of the delayed mineralization and the small
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amount of mineralized tissue [49,50]. Loss of trabecular bone and reduction of cortical bone thickness are observed [51]. Consequently, deformities are observed and the fracture risk is increased. Ciarelli et al. examined mineralization levels in cancellous bone of the iliac crest in individuals with and without vertebral fractures. They found that both groups had a similar mean bone formation rate, but the distribution of mineralization differed greatly. This finding supports the great influence of bone mineralization in vertebral fracture etiology and the variability of mechanical properties in the trabecular bone of individuals with vertebral fractures [52,53]. The clinical manifestations of patients with osteomalacia include muscle weakness, increased fall risk, and diffuse bone pain. These findings cannot easily distinguish osteoporosis from osteomalacia and patients suffering from acute vertebral fracture [54,55]. Vitamin D deficiency or insufficiency is present in approximately 1 billion people around the world. Although there is no consensus on optimal levels of vitamin D, deficiency is defined as serum levels lower than 20 ng/mL. A serum 25(OH)D3 level between 21 and 29 ng/mL indicates a relative insufficiency, whereas values greater than 30 ng/ mL are considered adequate [56]. In our study, there was statistically significant difference between the two groups in serum levels of 25(OH)D. The group that did not suffer from recurrent fractures after kyphoplasty had significantly higher levels of 25(OH)D compared with the fracture group. Also, higher NTx values were observed in the fracture group (Table 4). Additionally, it should be mentioned that patients who were receiving antiosteoporotic treatment and Ca/vitamin D supplements had statistically significant elevated levels of 25 (OH)D (15.9367.01 vs. 23.0765.5; p5.001) compared with those who did not, implying the protective value of antiosteoporotic treatment. Cement leakage is one of the most common complications of kyphoplasty and vertebroplasty. It has been reported in 3% to 27% of treated vertebrae with vertebroplasty and 8.6% to 27% with kyphoplasty [57]. In our study, this complication arises to 17.5% of overall treated patients, whereas the incidence was 12.9% and 33.3% for the group without fracture postoperatively and the group with recurrent fractures, respectively. It should be mentioned that in all cases the leakage was asymptomatic and occurred in the intradiscal space. According to the literature, intradiscal leakage of the cement may predispose to an increase in adjacent level fracture [20,26,58,59]. The leakage of the stiff cement into the degenerated disc of an osteoporotic spine conducts increased stress with altered force distribution on the end plate of the adjacent vertebrae. This is also indicated in our study, where the risk of new vertebral fractures was 7.96 times higher in kyphoplasties with cement intradiscal leakage than in kyphoplasties without. A limitation of the study is its relative small sample size, which, however, can be attributed to the strict inclusion and exclusion criteria that led to a homogenous patient sample
with all the advantages that this could carry. In addition, the possible negative impact of the relatively small sample size may be neutralized by the positive impact of the long follow-up period, which allowed the adequate evaluation of the incidence of recurrent fractures. However, the relatively small sample size may have underestimated a possible impact on the incidence of recurrent fractures of the other variables, which in the present study did not show a significant impact. It has to be emphasized that our data that imply that vitamin D plays a significant role in the development of recurrent fractures in the postkyphoplasty patients are only preliminary, but further larger and ideally prospective blinded studies would be needed to draw strong conclusions. In summary, the present study sheds light on the significance of the evaluation of bone metabolism as a part of the baseline checkup of the patients with vertebral compression fractures and the identification of risk factors with clinical importance for recurrent fractures after the augmentation techniques.
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