DOI 10.1007/s00198-014-2774-6 ORIGINAL ARTICLE Secondary prevention of osteoporotic fractures: evaluation of the Amiens University Hospital s fracture liaison service between January 2010 and December 2011 N. Dehamchia-Rehailia & D. Ursu & I. Henry-Desailly & P. Fardellone & J. Paccou Received: 17 March 2014 /Accepted: 11 June 2014 # International Osteoporosis Foundation and National Osteoporosis Foundation 2014 Abstract Summary The main goal was to assess the performance of the fracture liaison service (FLS) at Amiens University Hospital for 2 years. Osteoporosis medication was prescribed in 182 patients and 67.4 % were still taking treatment 18 months later. Secondary prevention of osteoporotic fractures has improved since the creation of the FLS. Introduction The main goal of the present study was to assess the performance and results of the FLS at Amiens University Hospital, France. Methods This was an observational, single-center, ambispective study. All patients admitted to Amiens University Hospital between January 2010 and December 2011 for a low-trauma fracture (vertebral and non-vertebral fractures) were identified by a FLS nurse. Patients willing to enter the study were assessed for their osteoporosis risk factors, daily calcium intake, bone mineral density (BMD) by DXA, and clinical chemistry parameters. When indicated, the patients received a prescription for osteoporosis medication. The participation rate, type of osteoporosis medications, initiation rate, and osteoporosis treatment persistence 12 and 18 months later were assessed. Results Of the 1,439 patients contacted, 872 were eligible for inclusion. A total of 335 patients (participation rate 38.4 %) were included in the study (mean age 63.3 years; 71.9 % female). All patients underwent BMD measurement, and N. Dehamchia-Rehailia: D. Ursu : I. Henry-Desailly : P. Fardellone: J. Paccou (*) Department of Rheumatology, Amiens University Hospital, 80054 Amiens, France e-mail: julienpaccou@yahoo.fr P. Fardellone: J. Paccou INSERM U1088 Pathophysiological mechanisms and consequences of cardiovascular calcification: role of cardiovascular and bone remodelling, Amiens University Hospital, Avenue René Laennec, 80054 Amiens, France more than 90 % of them were assessed for osteoporosis risk factors and daily calcium intake. Osteoporosis medication was prescribed in 182 (75.5 %) of the patients in whom it was indicated (n=241). The main class of osteoporosis medications prescribed was bisphosphonates (83.5 %), and 74.1 and 67.4 % of treated patients were still taking treatment 12 and 18 months later, respectively. The main cause of treatment discontinuation was non-renewal of the prescription by the patient s general practitioner. Conclusion Secondary prevention of osteoporotic fractures in Amiens University Hospital has improved since the creation of the FLS, with encouragingly high treatment initiation and persistence rates. Keywords Fracture. Fracture liaison service. Osteoporosis. Persistence Introduction Osteoporotic fractures are common, as more than 50,000 hip fractures occur each year in France in women aged 40 years or higher [1]. The incidence of hip fractures in subjects over the age of 39 years has decreased by 8 % in women (3,356 and 3,093 per million inhabitants in 2002 and 2008, respectively) and has increased by 4 % in men (1,131 and 1,172 per million inhabitants in 2002 and 2008, respectively) [1]. Osteoporotic fractures are associated with increased morbidity and mortality and impaired quality of life [2 4]. Furthermore, patients with an incident fracture have an increased risk of refracture [4]. In a recent study conducted in Australia, within 5 years following an initial fracture, 24 % of women and 20 % of men refractured and total mortality was 39 % in women and 51 % in men [4]. Bisphosphonates and other drugs can reduce the incidence of new vertebral fractures, new hip fractures, and new non-hip non-vertebral fractures in patients diagnosed
with osteoporosis [5 8]. In another study, annual infusion of zoledronic acid within 90 days after repair of a low-trauma hip fracture was associated with improved survival [9]. Screening high-risk patients by measuring bone mineral density (BMD) by DXA and/or using FRAX is endorsed by current guidelines [10 12]. Over the past 10 years, fracture liaison services (FLS) have been set up in several countries [13 16]. Typically, a nurse identifies men and women over 49 years with low-trauma fractures, and patients are screened by performing DXA and, if necessary, are then treated in an outpatient setting or FLS treatment advice is given to the general practitioner (GP) [13 16]. Fully coordinated, intensive models of care for secondary fracture prevention are more effective in improving patient outcomes than approaches involving alerts and/or education only [14]. For example, a Dutch study based on 337 patients revealed that 88 % of patients were still persistent with treatment 12 months after initiation of osteoporosis medication [15]. An FLS has been set up at Amiens University Hospital since 2006. However, our practice has not been previously evaluated and a new nurse started working in our FLS at the end of 2009. We present the results of a telephone survey conducted among patients included in the program between January 2010 and December 2011 with a minimum follow-up of 18 months. We therefore investigated the tracking and outcome of patients attending our hospital with low-trauma fractures. Osteoporosis treatment initiation, osteoporosis treatment persistence at 18 months, compliance, and subsequent fractures were also monitored. Materials and methods Fracture liaison service organization The study population was composed of adults of both genders, with no age limit, admitted to Amiens University Hospital between January 2010 and December 2011 for a low-trauma fracture and managed in our FLS. Patients were identified by an FLS nurse, using electronic medical records from the emergency and orthopedic surgery departments. Hip and spine BMD measured by DXA (QDR machines, Hologic Inc., Discovery W, Waltham, MA, USA, in 127 patients or DPX densitometers, GE Lunar, Prodigy, Madison, WI, USA, in 208 patients) and assessment of daily dietary calcium intake, a laboratory workup (including creatinine, calcium, phosphorus, 25-OH vitamin D3, intact parathyroid hormone), and a medical consultation with a physician were performed in all patients. WHO criteria were used to define osteoporosis (Tscore 2.5) and osteopenia (T-score between 1.0 and 2.5) in post-menopausal women. These criteria were also used for men 50 years old. There is no agreed definition of osteoporosis in pre-menopausal women and men <50 years old. The International Society for Clinical Densitometry recommends using Z-score, and women and men with Z-scores< 2.0 have been defined as having a bone density that is below the expected range for age. Pre-menopausal women and men <50 years old having a bone density with Z-scores< 2.0 and the presence of a low-trauma fracture have been defined as having osteoporosis. As recommended, the term osteopenia should be avoided in pre-menopausal women and men <50 years old and has not been used in this study. Risk factors for osteoporosis were also collected: low body mass index (<19 kg/m 2 ), current smoker, current alcohol abuse ( 3 units of alcohol per day for men and 2 units for women), previous low-trauma fracture, and family history of osteoporosis. Patients Between January 2010 and December 2011, 872 of the 1,439 patients identified by the FLS nurse were eligible and 567 patients were not eligible for one of the following reasons: death (n=16), lived too far away from hospital (n=22), known osteoporosis already on treatment (n=133), and severe cognitive disorders (n=396). Five hundred thirty-four (n=534) of the 872 patients did not attend the FLS unit for one of the following reasons: refusal (n=396) and agreed but subsequently failed to attend (n=138) (Fig. 1). A total of 338 patients were referred to our rheumatology department by the FLS after sustaining a low-trauma fracture. Three patients were also excluded after medical assessment, DXA, and laboratory workup: two patients had primary hyperparathyroidism and one was a pregnant woman. The participation rate was 38.4 % (335 of the 872 eligible patients were included) (Fig. 1). Study procedure Between May 2013 and October 2013, patients were contacted by phone to complete an evaluation questionnaire. When patients were unable to answer the questions, a family member or GP was interviewed instead. The questionnaire included closed-ended questions: (1) actual initiation of treatment or failure to initiate treatment, treatment prescribed, and initial coprescription of calcium and/or vitamin D supplementation; (2) treatment persistence, which only concerned patients who had actually initiated treatment, or the reasons for stopping or switching treatment; (3) treatment adherence as reported by the patients, which only concerned patients who continued treatment: good adherence when drug intake omission was unusual, intermediate adherence when drug intake omission was recurrent (less than half of the time), and poor adherence when drug intake omission was very common (more than half of the time); and (4) new incident fracture.
Fig. 1 Study population flow chart Ini al sample. Emergency and orthopedic department records 1439 872 Pa ents excluded 16 deaths 396 pa ents with cogni ve impairment 22 lived too far away from the hospital 133 known osteoporosis already treated Eligible pa ents 396 refused 138 ini ally agreed, but failed to a end 338 A ended baseline clinical visit 1 pregnant woman 2 pa ents with primary hyperparathyroidism 335 Pa ents included Statistical analysis Statistical analysis was performed using SAS software (version 8.2, SAS Institute Inc., Cary NC, USA). Descriptive statistics used for quantitative parameters were the mean, standard deviation, and minimum, maximum, median, and missing values; those used for qualitative parameters were frequency and percentage. All tests were two-sided, with a limit of significance of p<0.05. The various groups were compared using chi-square test or Fisher s exact test for categorical variables and either analysis of variance (or Student s t test for two groups) or Kruskal Wallis test (or Wilcoxon s rank test for two groups) for continuous variables. Kaplan Meier survival analysis of persistence was performed. Results Characteristics of all patients attending the FLS The mean age of the 335 patients attending the FLS was 63.3 ±13.9years,and241(71.9%)werewomenversus94 (28.1 %) men. The mean interval between onset of the fracture and the FLS visit was 5±4 months. Fifty-three patients (15.8 %) were younger than 50 years (31 pre-menopausal women and 22 men). Osteoporosis (Z-score< 2.0 and the presence of a low-trauma fracture) was diagnosed in 9.4 % of patients in this group. The fractures most commonly observed in patients younger than 50 years were ankle fracture (37.7 %) and wrist fracture (24.5 %), whereas shoulder and hip fractures were unusual (5.7 and 3.8 %, respectively). Two hundred eighty-two (84.2 %) patients were 50 years (210 menopausal women and 72 men). Osteoporosis (T-score 2.5) and osteopenia (T-score between 1.0 and 2.5) were diagnosed by DXA in 36.3 and 44.5 % of patients in this group, respectively. The fractures most commonly observed in patients 50 years old were hip fracture (28.4 %) and wrist fracture (27.7 %) followed by ankle and shoulder fractures (16.0 and 10.7 %, respectively). Demographic characteristics, fracture sites, and DXA results are summarized in Table 1. For the 335 patients attending the FLS, a mean calcium intake of 912±474 mg/day was recorded, and 43 % of them had a serum 25-OH vitamin D level less than 10 ng/ml, while 48 % had a serum 25-OH vitamin D level between 10 and 30 ng/ml. Specific osteoporosis treatment was indicated in 241 patients (mean age of 70.6±16.1 years and only 20 of them were younger than 50). Demographic characteristics, osteoporosis risk factors, and fracture sites are summarized in Table 2. Patients in whom osteoporosis treatment was indicated by the physician were older (p<0.0001) and more often women (p=0.04). The fractures most commonly observed were hip fracture (30.1 %) and wrist fracture (26.5 %). No patient was recruited for vertebral fracture. Ankle fracture was more common in patients in whom osteoporosis treatment was not indicated (37.8 versus 11.6 %, p<0.0001). Baseline clinical, BMD, and treatment characteristics Specific osteoporosis treatment was indicated in 241 patients (mean age of 70.6±16.1 years) but was only documented and
Table 1 Demographic data and relevant fracture sites of patients <50 years old compared to patients 50 years old All patients (n=335) Patients <50 years old (n=53) Patients 50 years old (n=282) p value Age, years (mean±sd) 63.3±13.9 41.4±5.8 67.4±10.9 <0.0001 Female gender, n (%) 241 (71.9) 31 (58.5) 210 (74.7) 0.02 Fracture type Hip, n (%) 82 (24.5) 2 (3.8) 80 (28.4) <0.0001 Wrist, n (%) 91 (27.2) 13 (24.5) 78 (27.7) 0.22 Shoulder, n (%) 33 (9.5) 3 (5.7) 30 (10.7) 0.32 Ankle, n (%) 65 (18.8) 20 (37.7) 45 (16.0) <0.0001 Osteoporosis a, n (%) 107 (31.9) 5 (9.4) 102 (36.2) <0.0001 a WHO criteria were used to define osteoporosis (T-score 2.5) in post-menopausal women and men 50 years old. Pre-menopausal women and men <50 years old having a bone density with Z-scores< 2.0 and the presence of a low-trauma fracture have been defined as having osteoporosis prescribed in 182 (75.5 %) patients (only 14 of them were younger than 50). Among the 59 remaining patients, 4 patients refused to take bisphosphonates, 51 patients in whom osteoporosis treatment was not initiated were lost to follow-up, treatment was initiated but not documented in 3 patients, and only calcium and vitamin D supplementation was initiated due to renal failure for 1 patient. Demographic characteristics, fracture sites, and DXA results are summarized in Table 3. No significant differences were observed between patients in whom osteoporosis treatment was or was not prescribed (p>0.05 for all; see Table 3). Osteoporosis treatment prescribed was oral or intravenous bisphosphonate (n=152, 83.5 %): risedronate (n=68, 37 %), alendronate (n=65, 36 %), zoledronic acid (n=11, 6 %), or ibandronate (n=8, 4 %). Treatment with zoledronic acid was prescribed but not initiated in four patients. Twenty-nine patients (16 %) initiated treatment with strontium ranelate, and one patient (1 %) initiated treatment with raloxifene (Fig. 2). No patient was treated with teriparatide. Treatment persistence, adherence, treatment switch, and subsequent fractures at 18 months Follow-up data were available for 166 patients, and no data on treatment duration were available for 16 patients (seven patients died and nine were lost to follow-up). One hundred twenty-three (74.1 %) of these patients were persistent with treatment after 12 months, and 112 (67.4 %) were persistent Table 2 Demographic data and relevant baseline characteristics of the 335 patients included All patients (n=335) Osteoporosis treatment indicated yes (n=241) Osteoporosis treatment indicated no (n=94) p value Age, years (mean ± SD) 63.3±13.9 70.6±16.1 54.3±12.3 <0.0001 Female gender, n (%) 241 (71.9) 181 (75.1) 60 (63.8) 0.04 Osteoporosis risk factors Body mass index <19 kg/m 2 (%) 5.0 6.6 1.0 <0.05 Smoking (%) 26.8 24.7 31.8 0.20 Alcohol abuse (%) 14.8 15.0 14.4 0.90 Previous low-trauma fracture (%) 27.1 33.7 10.0 <0.0001 Family history of osteoporosis (%) 5.5 4.6 7.6 0.29 Number of fractures 344 249 95 Major fractures a, n (%) 128 (37.2) 115 (46.1) 13 (13.6) <0.0001 Fracture type Hip, n (%) 82 (23.8) 75 (30.1) 7 (7.3) <0.0001 Wrist, n (%) 91 (26.4) 66 (26.5) 25 (26.3) 0.88 Shoulder, n (%) 33 (9.5) 29 (11.6) 4 (4.2) 0.03 Ankle, n (%) 65 (18.8) 29 (11.6) 36 (37.8) <0.0001 Osteoporosis b, n (%) 107 (31.9) 107 (44.4) 0 (0) <0.0001 a Major fractures: hip, spine, pelvis, shoulder, lower extremity of femur, upper extremity of tibia and three adjacent rib fractures b WHO criteria were used to define osteoporosis (T-score 2.5) in post-menopausal women and men 50 years old. Pre-menopausal women and men <50 years old having a bone density with Z-scores< 2.0 and the presence of a low-trauma fracture have been defined as having osteoporosis
Table 3 Demographic data and relevant baseline characteristics of patients in whom osteoporosis treatment was or was not prescribed Treatment prescribed yes (n=182) Treatment prescribed no (n=59) p value Age, years (mean±sd) 66.5±12.7 67.7±14.0 0.54 Female gender, n (%) 134 (73.6) 47 (79.6) 0.35 Body mass index <19 kg/m 2 (%) 5.0 11.8 0.08 Smoking (%) 24.1 26.9 0.68 Alcohol abuse (%) 15.4 13.4 0.72 Previous low-trauma fracture (%) 34.6 30.7 0.60 Family history of osteoporosis (%) 6.1 0 0.12 Number of fractures 188 61 Major fractures a, n (%) 88 (46.8) 27 (44.2) 0.73 Fracture type Hip, n (%) 60 (31.9) 15 (24.4) 0.28 Wrist, n (%) 49 (26.0) 17 (27.8) 0.78 Shoulder, n (%) 22 (11.7) 7 (11.4) 0.96 Ankle, n (%) 22 (11.7) 7 (11.4) 0.96 Osteoporosis b, n (%) 78 (42.8) 29 (49.2) 0.40 a Major fractures: hip, spine, pelvis, shoulder, lower extremity of femur, upper extremity of tibia and three adjacent rib fractures b WHO criteria were used to define osteoporosis (T-score 2.5) in post-menopausal women and men 50 years old. Pre-menopausal women and men <50 years old having a bone density with Z-scores< 2.0 and the presence of a low-trauma fracture have been defined as having osteoporosis after 18 months (Fig. 3). Twenty percent of patients (n=33) discontinued osteoporosis treatment during the first 6 months. Data on drug intake at 18 months were available for 95 patients, and treatment adherence was considered to be good for 89 (94 %) of them. During follow-up, 14 patients switched to other osteoporosis treatments as follows: risedronate (n=8), strontium ranelate (n=3), zoledronic acid (n=2), and alendronate (n=1). Eight of the 112 persistent patients (7 %) experienced a subsequent fracture: wrist fractures (n=2), ankle fractures (n =2), vertebral fracture (n =1), shoulder fracture (n=1), hip fracture (n=1), and rib fractures (n=1). Reasons for non-initiation, switching, or discontinuation of treatment Reasons for non-initiation, switching, or discontinuation of osteoporosis treatment are summarized in Table 4. The main adverse effects observed were gastrointestinal (diarrhea, abdominal pain), dental (gingival bleeding, dental pain), Fig. 2 Typesofosteoporosis medications Types of osteoporosis medications (%) 6 4 16 1 37 Risedronate Alendronate Zoledronic acid Ibandronate Stron um ranelate Raloxifene 36
Propor on of pa ents Time (months) Fig. 3 Kaplan Meier survival analysis of persistence dizziness, and skin rashes. No cases of osteonecrosis of the jaw or atypical fractures were reported. Discussion Secondary prevention of osteoporotic fractures constitutes a public health priority [12, 17]. The main objective of secondary prevention was to break the fracture cycle and reduce the morbidity and mortality associated with these fractures [18, 19]. The present study evaluated the efficacy of secondary prevention in the Amiens University Hospital s FLS over a 2- year period. Between January 2010 and December 2011, 335 patients with a low-trauma fracture were evaluated. All patients underwent BMD by DXA, and osteoporosis risk factors and daily calcium intake were assessed in more than 90 % of them. Osteoporosis treatment (mainly bisphosphonates) was prescribed in 75.5 % of these patients and was maintained at 18 months in 67.4 % of patients. The inclusion criteria adopted by our FLS do not comprise any age limit, while most models of secondary prevention have set this limit at 50 years [13 15, 20 24]. For the younger patients (<50 years old), several fractures recorded are probably not fragility fractures (particularly for ankle fractures), and osteoporotic treatment has not been indicated for most of these patients. The mean age of the patients in this study was therefore 63.3 years versus 66.4 to 72.9 years for other FLS units [13 15, 24]. The proportion of women in this study (71.9 %) did not differ from that reported in other studies, although some women in our study were premenopausal, in contrast with the recruitment of other FLS units [13, 25]. Among the patients identified by the FLS nurse, 27.5 % was not included because of cognitive impairment. No treatment was initiated in these patients, who presented a particularly high risk of falling and refracture. However, effective treatments are available for this population. The antifracture efficacy of zoledronic acid after hip fracture has recently been demonstrated in elderly patients with cognitive impairment [26]. Denosumab could be another alternative in these patients, especially those with renal failure [27]. The mode of administration of these two treatments is more suitable for these frail patients. The patient recruitment efficacy of the program was 38.4 %, lower than that observed in other programs: 50.6 % in The Netherlands [15], 55.6 % in Spain [23], and 73.5 and 85 % in Great Britain [20, 21]. Patient recruitment by our center needs to be improved by better patient information and a shorter interval between the fracture and the FLS visit, as this interval is fairly long compared to the intervals reported by other FLS [13] and could explain why 138 patients agreed but subsequently failed to attend the FLS. Moreover, information about public health problems, particularly about osteoporosis, is inadequate in France, which probably explains why patients are not aware about the primary and secondary prevention of osteoporosis. No patient with vertebral fracture was recruited by our FLS. A low vertebral fracture rate has also been reported by other FLS centers with 7.9 % in Spain [23] and 8.3 % in The Netherlands [15]. Patient recruitment and patient management must be improved by better collaboration with emergency care physicians and radiologists. Moreover, vertebral fracture assessment technology is now available on newer bone Table 4 Causes for non-initiation, switching, or discontinuation of treatment Treatment prescribed but not initiated Treatment discontinued Treatment switched Number of patients, N 4 50 14 Fear or occurrence of adverse effects, n 12 6 Non-renewal of the prescription by the patient s GP,n 18 Polypharmacy, n 3 New fracture, n 1 No interest, n 4 Modalities of administration, n 3 3 1 Ibandronate delisted, n 3 Bad reputation of server, n 1 2 Missing data, n 1 6 1
densitometers and has been shown to increase vertebral fracture detection rates [28, 29]. This new technology must be implemented in order to identify the occult vertebral fracture population. All patients underwent baseline DXA assessment on inclusion. However, the need for DXA scanning in secondary prevention programs remains controversial. Nevertheless, DXA remains the current standard for monitoring the therapeutic effect [11, 30], and BMD testing was performed as part of the osteoporosis care program in the majority of secondary fracture prevention programs reviewed by the International Osteoporosis Foundation [17]. In the population of treated patients, 74.1 and 67.4 % were still taking treatment 12 and 18 months later, respectively. These results are similar to those reported by Streeten et al. with 65 % of patients still on treatment after 18 months [31] andremainsatisfactorycomparedtothosereportedby Boudou et al. with 80 % of patients on treatment after 12 months [13]. In a Dutch study, 88 % of patients were still persistent with treatment 12 months after initiation of osteoporosis medication [15]. However, survival analysis of persistence demonstrated that 20 % of patients discontinued osteoporosis treatment within the first 6 months. The main cause of treatment discontinuation was non-renewal of the prescription by the patient s GP. Active participation of the GP in the secondary prevention program may help to resolve this problem, and systematic follow-up visits during the first 6 months are also necessary. This study presents several limitations. Information obtained from patient questionnaires and interviews is associated with biases, missing data, and inaccurate accounts by patients. Patients with cognitive impairment who did not attend the FLS were not evaluated, and the falling risk was not assessed, although it represents a major risk for new fractures [24]. Treatment adherence was assessed by drug intake, but the questionnaire used, although easy to understand and rapidly completed, has not been validated. Underdiagnosis and undertreatment of osteoporotic fractures are prevalent worldwide. FLS run by healthcare coordinators have been shown to improve fracture care. The present study provides evidence of the potential success of a secondary fracture prevention program, including improved assessment and treatment rates. However, implementation of the program and the first 2 years of operation have identified certain problems and limitations associated with our program that constitute valuable learning points. The lessons learned will enable us to develop a revised and more effective program in the near future. Acknowledgments We would like to thank Corinne Fauvet and Alain Henocq for their technical assistance. Conflicts of interest None References 1. 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