Long-term prospective study of osteoporotic patients treated with percutaneous vertebroplasty after fragility fractures

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1 DOI /s z ORIGINAL ARTICLE Long-term prospective study of osteoporotic patients treated with percutaneous vertebroplasty after fragility fractures M. Mazzantini & P. Carpeggiani & A. d Ascanio & S. Bombardieri & O. Di Munno Received: 10 May 2010 /Accepted: 22 June 2010 # International Osteoporosis Foundation and National Osteoporosis Foundation 2010 Abstract Summary This paper presents a prospective study on factors that could influence fracture risk after percutaneous vertebroplasty (PVP) in 115 osteoporotic patients. The mean follow-up was 39 months. The incidence of new fractures after PVP was 27.8%. Low body mass index (BMI), bone mineral density (BMD), and vitamin D are factors associated with increased risk of new fractures. Introduction The purpose of this study was to evaluate factors that could increase the occurrence of new vertebral fractures (VFx) after PVP. Methods In our prospective study, we included patients of both sexes with osteoporosis (OP) and at least one painful VFx. We performed a baseline biochemical evaluation (including vitamin D plasma levels) and collected demographic, BMD, and clinical data. One hundred fifteen patients were treated with PVP and assigned to oral bisphosphonates plus Ca and vitamin D. The patients M. Mazzantini (*) : A. d Ascanio : S. Bombardieri : O. Di Munno Rheumatology Unit, Department of Internal Medicine, Ospedale S. Chiara, via Roma 67, Pisa, Italy mmazzant@int.med.unipi.it A. d Ascanio adascani@int.med.unipi.it S. Bombardieri s.bombardieri@int.med.unipi.it O. Di Munno odimunno@int.med.unipi.it P. Carpeggiani Neuroradiology Unit, University Hospital of S. Chiara, Pisa, Italy p.carpeggiani@ausl.mo.it returned to control visits after 1, 3, and 6 months and every 6 months thereafter. X-rays film of the dorsolumbar spine was repeated every 12 months, or in case of pain that would suggest VFx occurrence. Results The mean follow-up was 39±16 months (range, 15 79). Thirty-two patients (27.8%) had new fragility VFx, all symptomatic. All the fractured patients agreed to undergo a new PVP. We compared the patients who had new VFx to those who had not, and we found significantly lower BMI, total hip, and femoral neck T-scores in the group with new VFx. Furthermore, baseline plasma levels of 25(OH) vitamin D (25(OH)D) were significantly lower in this group. Upon analyzing plasma levels of 25(OH)D 12 months after PVP, we found that a significant difference still persisted: 22±12 (group with new VFx) vs. 41±22 ng/ ml (group with no VFx; p<0.01). Conclusion We found that in patients with OP treated with PVP, the incidence of new VFx was 27.8% after 39 months; low BMI, BMD, and vitamin D are factors associated with increased risk of new VFx in patients treated with PVP. Keywords Osteoporosis. Vertebral fracture. Vertebroplasty Introduction Vertebral fragility fractures are the most common consequence of osteoporosis. After occurrence of vertebral fracture, many patients experience severe debilitating back pain, causing a reduced quality of life and physical function that become permanent in a proportion of subjects. Conservative treatment consists of analgesia, bed rest, and bracing. Patients that are resistant to such treatment or present contraindication or side effects to analgesic treatment may be candidate to percutaneous vertebroplasty

2 (PVP), in which the fractured vertebra is stabilized by the injection into the vertebral body of cement, usually polymethylmetacrylate (PMMA). This procedure reportedly produces rapid and persistent relief from pain in most patients [1-3]. However, strengthening the treated vertebral body with cement infusion may lead to increased mechanical forces on the adjacent vertebrae, thereby predisposing to fractures [4, 5]. Incident fractures are reported after PVP, but a causal relationship is difficult to prove because patients with osteoporosis and vertebral fragility fractures develop additional fractures simply as a result of their underlying disease [6, 7]. This issue has been debated extensively in the literature with little consensus to date, with the exception of cases occurring after leakage of cement into the intervertebral disc [8]. A non-randomized controlled study reported a 24% incidence of new vertebral fractures after 2 years, comparable to that of patients treated conservatively [2]. Uncontrolled prospective [9-12] and retrospective [13] studies reported an incidence of fractures after PVP that ranges from 17% to 37% within 1 year of follow-up, and a retrospective population-based cohort study showed an increased rate of fracture with respect to patients not treated with PVP (18.9% and 9.8% after 1 year, respectively) [14]. In general, these findings are difficult to interpret because of the different population studied, the short follow-up period, and the lack of information about parameters of bone density and metabolism of the patients who underwent PVP and about antiosteoporotic medications after the procedure. Although randomized controlled clinical trials are clearly needed to better evaluate the longterm safety of PVP, longitudinal studies on a large sample of subjects with a long observational period may be of significant value in this field. We here report the result of a long-term prospective study on osteoporotic patients treated with PVP, aimed at assessing the occurrence of new vertebral fractures and variables associated with such adverse event. Patients and methods Patients The inclusion of patients into the follow-up program started on January 2002 and ended on August For the purpose of the present study, we considered for inclusion all consecutive patients of both sexes who had at least one painful vertebral fracture for which they had been referred to our units. Only osteoporotic patients were included: the diagnosis of osteoporosis was made on the basis of the fragility nature of the vertebral fractures and the evidence of a low bone mineral density (BMD), as assessed by doubleenergy X-ray absorptiometry (DXA) performed at vertebral and femoral sites, according to WHO criteria [15]. Only patients with a DXA T-score less than 1.0 at either sites were included into the follow-up. After a thorough anamnestic and clinical evaluation, any secondary form of osteoporosis was excluded, with the exception of glucocorticoid-induced osteoporosis. Furthermore, a baseline biochemical evaluation was made to exclude abnormality in calcium metabolism: plasma calcium, phosphorus, total alkaline phosphatase, 24-h urinary excretion of calcium, serum PTH, and plasma levels of 25(OH) vitamin D (25(OH)D). Patients with both insufficient and low 25 (OH)D levels (<20 ng/ml) were included only if they did not show any other biochemical alteration or personal history suggesting osteomalacia. Nonetheless, these patients were supplemented before the procedure of PVP with a single starting dose of 300,000 IU of vitamin D followed by 800 IU/day throughout the study period. Patients with normal vitamin D levels only received the daily supplementation. Individual calcium intake (dietary and supplemental) was routinely assessed and corrected to 1.2 g/day when insufficient. Previous treatment with PVP or kyphoplasty represented a reason for exclusion from this study. In addition to the above-mentioned parameters, the following data were collected: age, body mass index (BMI), smoke, previous diagnosis of osteoporosis, other fragility fractures, previous treatment of osteoporosis, time of painful vertebral fracture occurrence, duration of symptoms, number and level of other prevalent vertebral fractures, GC mean daily, and cumulative doses. To perform the procedure of PVP, the patients were hospitalized in the Rheumatology Unit of our Hospital and discharged the day after the procedure if no adverse event had occurred. The patients were informed about the benefit/risk ratio of the procedure of PVP, the possibility of an increased fracture risk, and the necessity of a strict follow-up program. After that, the patients gave their written informed consent to the procedure of PVP, which was approved by the local Ethics Committee. Pain Patients with primary or glucocorticoid-induced osteoporosis and painful vertebral fractures were deemed candidate to PVP if they had resting pain >50 mm on a 100-mm visuo-analogic scale (VAS) despite medical therapy or if they showed undesirable adverse effects to medical therapy. Pain management consisted of an individually tailored, 4-week, step-up course of paracetamol (3 g/day), paracetamol plus codeine ( mg each, three times a day), or any of the two plus NSAIDs or COXIBs or, finally, major opioids at the highest tolerated dose. This procedure resulted to be in accordance to recently published guidelines [16, 17].

3 Prevalent fractures An accurate clinical radiological correlation was a crucial step in patients selection for PVP. Antero-posterior and lateral X-rays of the dorsolumbar spine (T4 L5) were obtained at baseline for identifying the number and the site of prevalent fractures. A prevalent vertebral fracture was defined as a decrease of at least 20% in any vertical dimension, according to the Genant method [18]. A neuroradiologist (PC) and a rheumatologist (MM) examined X-rays concomitantly. Patient history or older radiological examinations served to differentiate chronic from acute compression fracture and to establish the time of the fracture event. Furthermore, all patients underwent magnetic resonance (MR) imaging study of the dorsolumbar spine due its sensitivity for bone marrow edema. Bone edema is defined as increased signal intensity at the T2-weighted and short tau inversion recovery images and decreased signal intensity at the T1-weighted images, and its detection suggests acute, subacute, and nonhealed fractures [19]. When MR was impossible to perform due to patient s unwillingness (one patient) or contraindication (three patients), we used a bone scan as an alternative to detect an increased tracer uptake, which is reported to predict a positive clinical response following PVP [20]. Patients candidate to PVP had to show spontaneous pain at the site of vertebral fracture identified on X-ray films, provoked pain after digital pressure on the same level during physical examination, and either bone marrow edema in MR imaging or increased uptake in bone scan. Finally, before performing the procedure of PVP, a limited computed tomography (CT) scan through the intended level was performed in order to assess the intactness of the vertebral walls. Technique of PVP All PVPs were carried out by the same operator (PC). The procedures were performed on local anesthesia and under fluoroscopy control. Some patients received premedication with morphine (1 mg). No sedation was used. All patients were fully monitored. Before starting treatment, the correspondence between radiological data and clinical data was verified by checking pain reaction to compression of spinous processes under fluoroscopy. We preferentially used 13G or 15G needles. The use of fine needles is less traumatic, it requires less anesthetics per level and no skin incision, and it facilitates the access into thin pedicle and vertebra plana. Through a monolateral access (transpedicular at lumbar level or parapedicular at thoracic level), the needle tip was centrally located to achieve a full filling of the vertebra at the midline from the upper to the lower endplate, with an average amount of injected cement of cm 3 in thoracic and 3 4 cm 3 in lumbar vertebrae. This technique allows multilevel treatment safely (Fig. 1). A different technique was adopted if fracture with osteonecrotic cleft was identified on MR imaging and CT. In this case, a bilateral approach or needle repositioning during the procedure was necessary to obtain complete filling of both the cleft and the remaining vertebral body. In this way, a complete fracture stability is achieved, and further collapse is avoided (Fig. 2). The treatments were very well tolerated, with a mean time procedure up to 60 min. Follow-up The patients were asked to return to control visits after 1, 3, and 6 months and every 6 months thereafter. The control visits were performed by the same physician (MM). The Fig. 1 Multiple low thoracic-lumbar fractures (from T11 to L5) are identified on computed tomography (a) with diffuse poor localized pain. All the seven vertebrae were treated in the same session with a monolateral approach (b). A good central vertebral filling is obtained at all levels (c)

4 Fig. 2 Fracture with osteonecrotic cleft: osteoporotic fracture with liquid cleft showed by magnetic resonance imaging (a). The cavity is surrounded by sclerotic bone reaction demonstrated by computed tomography, dividing the vertebral body in two compartments (b). One needle is inserted superiorly into the cleft and the other inferiorly into the remnant body part to achieve complete boy filling (c, d). The different appearance of the injected cement into the cleft (dense, well shaped) and in the remaining spongiosa (more diffuse) may be appreciated pre-planned mean follow-up period for the entire population was set at 36 months, with a minimum of 12 months for each patient. To assess the occurrence of new (incident) fracture, X-rays film of the dorsolumbar spine (T4 L5, anteroposterior and lateral views) were repeated every 12 months, or when a patient complained of vertebral pain that would suggest the occurrence of a fracture. For this purpose, we invited the patients to notify immediately by phone call any painful symptoms at the spine. An incident fracture was defined as an increased Genant s deformity grade of a vertebra, previously fractured or not. Only fragility fractures were considered. A neuroradiologist (PC) and a rheumatologist (MM) examined X-rays concomitantly. After 12 months, a new determination of plasma levels of 25(OH)D was performed. At each visit, the daily calcium intake (dietary plus supplemental) was investigated in order to maintain it above 1.2 g/day. At the moment of discharge from hospital, the patients were instructed to take weekly oral bisphosphonates (alendronate 70 mg or risedronate 35 mg). The choice of these two drugs was due to their almost equal efficacy in reducing fracture occurrence in osteoporotic patients and to the need of homogeneous therapy in the cohort in order to avoid treatment-related variability with regard to the main outcome. Both adherence and compliance to anti-fracture therapy were assessed at each follow-up visit. Patients, and their relatives when appropriate, were instructed to take note on a diary of every missed dose of the weekly bisphosphonate. After the execution of PVP, patients were allowed to take analgesic treatment, if needed, starting with paracetamol and then individually tailored if insufficient. Pain on visuoanalogic scale was recorded at each visit. Individual patient s data collection ended when one of the following events occurred: new vertebral fracture, withdrawal from alendronate and risedronate (switching from one to the other was permitted), or not presenting to two consecutive visits. Statistical analysis Data are expressed as mean±standard deviation. Primary endpoint was the cumulative incidence of new fragility vertebral fractures. In comparing variables between the patients who sustained a new vertebral fracture and those who did not, we used the t test to compare the calculated means, and patient proportions were compared by the χ 2 test. Changes from baseline in measures of pain and plasma levels of 25(OH)D were analyzed by the t test. Results From January 2002 to August 2007, 121 patients were treated with PVP and included into the follow-up program, which ended in December 2008 when the last patient who had been included returned to the 12-month visit. Six patients were excluded from the analysis: one died 4 months after PVP, two were lost to follow-up within the first year, two missed two consecutive control visits, and one developed cancer 6 months after PVP. We here report the results of 115 patients. In December 2008, the mean followup for the whole population was 39±16 months (range, 15 79). Table 1 shows the characteristics of the population. At baseline, the total number of fractured vertebrae was

5 Table 1 Characteristics of the 115 patients treated with vertebroplasty a Indication: rheumatoid arthritis n=11; systemic lupus erythematosus n=5; other connective tissue diseases n=5; polymyalgia rheumatica n=5; Horton s arteritis n=3; other systemic vasculitis n=4; BPCO n=7; myasthenia gravis n=3 b Subjects with documented vertebral fractures before the occurrence of those for which PVP was indicated c Available for 46 patients, due to fractures of more than one vertebral body within L1 L4 Female, no. (%) 93 (81%) Age, years 71±8 BMI 24.1±4.7 Current smokers, no. (%) 18 (16%) Glucocorticoid-induced osteoporosis, no. (%) a 43 (37%) Cumulative GC dose, g 8.2±2.2 Daily dose (6-methylprednisolone), mg 5.2±1.8 Pain score at rest, mm 80±10 Duration of symptoms, months 6±11 Percent taking NSAIDs/COXIBs 78% Percent taking opioids 17% Previous treatment of osteoporosis, no. (%) 34 (30%) Alendronate or risedronate, no. (%) 20 (17%) Other bisphosphonates, no. (%) 9 (8%) Raloxifene, no. (%) 3 (3%) Teriparatide, no (%) 2 (2%) Previous vertebral fractures, no. (%) b 21 (18%) Number of prevalent vertebral fractures 2.8±1.7 Previous non-vertebral fractures, no. (%) 18 (16%) Calcium intake, g/day 0.76±0.23 Total alkaline phosphatase, UI/L (normal values, ) 122±23 Plasma 25(OH)D levels, ng/ml (normal values, >20) 28±18 PTH, pg/ml (normal values, 20 68) 48±22 Spine L1 L4 T-score c -2.7±1.3 Total hip T-score -2.3±1.0 Femoral neck T-score -2.5± ; the mean number of prevalent vertebral fractures per patient was 2.8±1.7 (range, 1 8), and the mean Genant s score was 5.0±2.4 (range, 1 14). The time interval between the occurrence of the painful vertebral fractures and the execution of PVP was 6±11 months (range, 1 84). A total of 262 vertebral bodies were treated with PVP, with a mean number of treated vertebrae per patient of 2.3±1.6 (range, 1 8): 244 were fractured and 18 normal (ten patients). Normal vertebrae were preventively injected with PMMA if they were deemed at very high risk of fracture as located between two vertebrae collapsed and treated with PVP. Table 2 and Fig. 3 show data regarding prevalent fractures and the number of fractures treated with PVP. One vertebral body was treated in 50 patients, two in 24 patients, three in 22 patients,fourin7patients,fivein8patients,sevenin2patients, andeightin2patients. Pain One month after PVP, pain (VAS) was reduced significantly compared with baseline: 22±10 vs. 80±10 mm, respectively (p<0.001). This result was maintained throughout the observational period (data not shown). Correspondingly, the percentage of patients taking NSAIDs/COXIBs fell from 78% to 3%, and none of the patients needed opioids anymore, unless a new fracture had occurred. Incident vertebral fractures The aim of the study was to assess the incidence of new vertebral fractures, both radiological and clinical. Over a mean 36-month follow-up, 32 patients had new fragility fracture occurrence, signifying a cumulative incidence of 27.8%. All new fractures were clinically evident, in that the patients themselves contacted the physician immediately after having experienced new back pain: radiological examination revealed 75 new vertebral fractures (12 patients had one new fracture, 7 had two new fractures, 7 had three new fractures, 5 had four new fractures, and 1 had five new fractures) that involved vertebral bodies not previously fractured nor treated with PVP. The mean time interval between the PVP procedure and the onset of a new fracture was 12±9 months (range, 1 42). In particular, 8 patients sustained a new fracture within 1 month after PVP, 14 within the first 6 months, and 18 within the first 12 months. In 24 patients (68%), the new fracture was adjacent to a previously treated vertebral body: in half of these cases, the new fracture occurred in the superior

6 Table 2 Patients with one or multiple vertebral fractures at baseline No. of patients No. of fractures Genant s score 1 (%) Genant s score 2 (%) Genant s score 3 (%) > Distribution of Genant s score within each group Characteristics of the vertebral fractures adjacent vertebral body. Radiological investigation of the spine performed every 12 months in the asymptomatic patients did not reveal any additional vertebral fracture to those identified clinically. Of note, none of the 262 treated vertebrae showed reduction in vertical height that is worsening of their Genant s score. All the fractured patients agreed to undergo a new PVP. Incident non-vertebral fractures Non-vertebral fragility fractures occurred in eight patients (7%): one at the hip, one at the humerus, four at the ribs, one at the distal forearm, and one at the pelvis. Comparison between patients with and without new vertebral fractures With the hypothesis that baseline data may influence the occurrence of new vertebral fractures, we compared the patients who had new vertebral fractures during the follow-up to those who had not. Table 3 shows the differences between the two groups. We found significant differences with respect to BMI, No. of fractured vertebrae No. Of treated vertebrae D4 D5 D6 D7 D8 D9 D10 D11 D12 L1 L2 L3 L4 L5 Fig. 3 Characteristics of the vertebral fractures. Level of fractured (total number 322) and treated vertebrae (total number 244) total hip, and femoral neck T-scores, suggesting a more severe osteoporotic disease in those experiencing new fractures. Furthermore, baseline plasma levels of 25(OH)D were significantly lower in this group. Upon analyzing plasma levels of 25(OH)D in 107 patients 12 months after PVP, we found that a significant difference between the two groups still persisted: 22±12 (group with new fractures, n=30) vs. 41± 22 ng/ml (group with no fractures, n=77; p<0.01). After 12 months of vitamin D supplementation, 8/30 patients vs. 0/ 77 patients, respectively, had 25(OH)D levels below 12 ng/ml, which is considered the cut-off level for vitamin D deficiency. Compliance to medical antiosteoporotic therapy (weekly alendronate or risedronate plus daily calcium and vitamin D) was high and similar in the two groups, with more than 90% of doses taken, as assessed by means of interview at each control visit (calcium and vitamin D) and by count of doses missed (alendronate and risedronate). Discussion We found a 27.8% cumulative incidence of new vertebral fractures, symptomatic, in a cohort of 115 patients treated with PVP and followed for a mean of 39 months. Eighteen of 32 patients had a new vertebral fracture within 1 year after PVP; 68% of the new fractures occurred in a vertebral body next to one treated with PVP. Although there are no studies of similar length in literature to make a comparison, the incidence of 27.8% over 39 months of follow-up seems to be favorable with respect the others reported in literature. Prospective studies reported an incidence of new fractures of 24 37% after 12 months of follow-up [11-13], Kobayashi et al. reported an incidence of 18% after 15 months [10], and Diamond et al. reported a 24% of new fractures after 24 months [2]. In general, higher rate of new fractures is reported by studies in which an imaging follow-up program had been scheduled [11, 12]. The relatively lower incidence of re-fracture in our population could be the consequence of the careful monitoring of antiosteoporotic treatment: at each visit, daily calcium vitamin D intake and bisphosphonate treatment were thoroughly

7 Table 3 Comparison of baseline characteristics between those who developed new vertebral fractures and those who did not With new vertebral fracture (n=32) Without new vertebral fractures (n=83) P Female, no. (%) 26 (81%) 67 (81%) NS Age, years 72±6 71±8 NS BMI 22.6± ± Current smokers, no. (%) 7 (22%) 11 (14%) NS GC-induced osteoporosis, no. (%) 12 (38%) 31 (37%) NS Cumulative GC dose, g 7.5± ±2.0 NS Pain score, mm 83±9 80±9 NS Previous treatment of osteoporosis, no. (%) 12 (38%) 22 (27%) 0.02 Prevalent vertebral fracture 2.7± ±1.7 NS Mean Genant s score 4.8± ±2.4 NS Previous non-vertebral fracture 4 (13%) 12 (14%) NS Time from fracture to PVP, months 5±6 6±10 NS No. of vertebral bodies treated with PVP 2.0± ±1.7 NS Calcium intake, g/day 0.72± ±0.23 NS Total alkaline phosphatise, UI/L 132±30 115±20 NS Plasma 25(OH)D levels, ng/ml 14±9 38± PTH, pg/ml 52±26 46±18 NS Spine L1 L4 T-score a -3.3± ±0.9 NS Total hip T-score -3.2± ± Femoral neck T-score -3.1± ± a Available for 16 and 30 patients of the two groups, respectively investigated. Therefore, the compliance to anti-fracture therapy of our patients was very high, with more than 90% of the daily calcium and vitamin D and weekly doses of bisphosphonates actually taken. Nonetheless, there is a striking difference between the 27.8% incidence of new vertebral fractures in our study and the incidence of new vertebral fractures reported in randomized controlled studies that used alendronate and risedronate to prevent recurrent fractures with a comparable length of follow-up: 8.0% and 13.4% with alendronate [21, 22] and 11.3% and 18.1% with risedronate [23, 24] after 36 months of treatment. These two drugs have been shown to nearly halve the occurrence of new vertebral fractures. The characteristics of our osteoporotic patients (e.g., mean age and number of prevalent fractures) were quite similar to those of the patients enrolled into these randomized controlled trials. An exception is the involvement of patients with glucocorticoid-induced osteoporosis (43 patients, 37% of our sample). However, occurrence of re-fracture in the GC-treated group was similar to that observed among patients with primary osteoporosis. Furthermore, the suspicion that PVP could increase the risk of new vertebral fractures comes from two additional considerations. First, 68% of the new fractures occurred near a vertebral body treated with PVP. This is in line with previous report of % of adjacent level fractures after PVP [2, 9-12]. Second, non-vertebral fractures occurred in only 7% of the patients, and in as few as 3.5% of the patients if we exclude rib fractures. This remarkable difference in site-specific fracture rates (vertebral, 27.8%; major non-vertebral sites, 3.5%) after 39 months may raise the hypothesis that PVP represents a risk factor of vertebral fractures. However, we have to take into consideration that the patients with vertebral fractures who suffer pain resistant to conservative therapy and for this reason, they are judged to be candidate to PVP may represent a group with a risk profile of subsequent fractures different from those whose vertebral pain decline with time. Furthermore, those who experienced a new fracture were particularly at risk for subsequent fractures: they showed lower BMI, had a more severe reduction of BMD, and showed lower baseline and 12-month plasma levels of vitamin D. In a retrospective analysis of risk factors for new vertebral fractures after PVP, Lin et al. found that BMI was significantly associated with new fractures [25], which suggested osteoporosis as a mechanism of fracture. Vitamin D deficiency-insufficiency is a well-known determinant of fractures, both vertebral and non-vertebral. We provided a dose of 300,000 IU of vitamin D to the patients who had baseline plasma levels of 25(OH)D<20 ng/ml and 800 IU of vitamin D to all the patients after PVP, but these doses were not sufficient in

8 subgroups of subjects: after 12 months, re-evaluation of vitamin D plasma levels showed significantly lower mean values among those who had new fractures. In particular, 43% of the patients with new fractures and only 8% of those fracture-free had values <20 ng/ml. These results include two practical implications: first, a supplementation of 800 IU/day may be insufficient to achieve adequate protection against fracture in some individuals, so that either higher daily doses and earlier reassessment of plasma levels of vitamin D would be advisable in subjects treated with PVP; second, bisphosphonates may be insufficient in reducing fracture risk in patients treated with PVP that show very low T-score values, and anabolic therapy with teriparatide may be of greater efficacy in such patients. Randomized controlled trials on PVP with new vertebral fractures as primary outcome are needed. Recently, the efficacy of PVP in reducing pain and improve disability has been questioned by two randomized controlled trials [26, 27], at least in the short-term. This casts doubts on the generally held belief that PVP is helpful on the long-term in patients with painful vertebral fractures. On the other hand, we underline that all the patients in this study who sustained a new vertebral fracture after PVP expressed their willingness to undergo a second PVP. We presume that this could be a reflection of a significantly perceived benefit, even though temporary. In conclusion, we report that in patients with osteoporosis (primary and glucocorticoid-induced) followed for a mean of 39 months, the incidence of new vertebral fracture after PVP was 27.8%; low BMI, low BMD, and vitamin D insufficiency or deficiency are factors associated with the risk of new fractures in patients treated with PVP. 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