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Declining trends in the incidence of hip fractures in people aged 65 years or over in years 2000–2011
EJINME-03247; No of Pages 6 European Journal of Internal Medicine xxx (2016) xxx–xxx
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Original article
Declining trends in the incidence of hip fractures in people aged 65 years or over in years 2000–2011 Sandro Giannini a,⁎, Stefania Sella a, Maurizio Rossini b, Daniela Braghin a, Davide Gatti b, Maria Teresa Vilei a, Annalisa Amabile a, Maria Fusaro c, Anna Chiara Frigo d, Giuseppe Sergi e, Roberto Lovato f, Martino Nobile a, Fabrizio Fabris a, Silvano Adami b a
Clinica Medica 1, Department of Medicine, University of Padova and Regional Center for Osteoporosis, Padova, Italy Rheumatology Unit, Department of Medicine, University of Verona and Regional Center for Osteoporosis, Verona, Italy c Institute of Clinical Physiology, National Council of Research, Pisa, Italy d Department of Cardiac, Thoracic and Vascular Sciences, University of Padova, Italy e Geriatrics Division, Department of Medicine, University of Padova, Italy f Osteoporosis Center, Casa di Cura Villa Berica, Vicenza, Italy b
a r t i c l e
i n f o
Article history: Received 22 March 2016 Received in revised form 27 May 2016 Accepted 7 June 2016 Available online xxxx Keywords: Hip fracture incidence Hospitalization Osteoporosis Aging
a b s t r a c t Background: The aim of this study was to explore hip fracture (HFx) incidence in the Veneto Region of Italy, looking at potential differences with the national data. Methods: We analyzed HFx incidence for people aged 65 years or over, in years 2000–2011, using data from the Regional Hospitalization Database. Patients were stratified by sex, calendar year and 5-year age class. Data for the single provinces of the Region were also obtained. Absolute number of HFx, crude incidence for 10,000 inhabitants and age-standardized fracture rates were calculated. Results: During the study period, there were 53,917 hospitalizations for HFx (77.7% in females). In the whole 11 year period of observation, the absolute HFx number increased by 17.7% in males and 10.6% females, respectively. However, age-standardized incidence rates declined by 18% in the same period (IRR 0.82, 95% CI 0.78– 0.87). This decreasing trend was almost identical through all the age-cohorts up to 84 years. In the whole study period, HFx incidence was lower for Padova (IRR 0.63, 95% CI 0.60–0.66) and Verona (IRR 0.66, 95% CI 0.63–0.70) provinces as compared to the others. This regional profile was quite different with respect to the data published, for the same calendar years, for Italy as a whole, in spite of an almost identical demography of the population. Conclusions: HFx incidence is declining in the Veneto Region of Italy. Further studies, aimed to investigate factors involved in this figure are needed. © 2016 Published by Elsevier B.V. on behalf of European Federation of Internal Medicine.
1. Introduction Osteoporosis and related fractures are very common in the elderly and represent one of the most important causes of morbidity and mortality [1–3]. In year 2010, 3.5 million new fragility fractures were sustained in the EU countries, comprising 620,000 hip fractures, with an economic burden estimated at €37 billion [4,5]. In recent years, several studies have been carried out to investigate current trends in hip fracture incidence. While some of these studies have reported a substantial leveling-off or even a decrease in age-adjusted incidence of hip fractures [6–20], a further trend toward an increase has been described ⁎ Corresponding author at: Clinica Medica 1, Department of Medicine, Regional Center for Osteoporosis, University Hospital of Padova, Via Giustiniani, 2, 35128 Padova, Italy. Tel.: +39 049 8212169; fax: +39 049 8214459. E-mail address: [email protected] (S. Giannini).
by others [21–30]. In addition, such opposite trends have been observed in countries of the same region of the world or even within the same nation [23–25]. No definite explanations have been provided for such contrasting evidences, but different cohort or period effects could be involved [17]. According to year 2011 demographic data, Italy ranks second among European Countries for the aging index, that is a composite demographic ratio defined as the percentage between the old age population (over 65) and the young population (under 15), falling just behind Germany (147% and 154%, respectively) [31]. Due to the increasing bone fragility induced by age, a rise in hip fractures should be expected. Trends in hip fracture have been explored in Italy for the period 1999–2009 [21,26–30]. In year 2005, 94,471 patients aged 65 + years were hospitalized due to hip fractures in Italy, with an increase of 28.5% as compared to year 2000 [29]. In the same period, hospitalization costs increased by 36.1%, reaching 467 million euros in 2005. More recently, Piscitelli et al. [30]
http://dx.doi.org/10.1016/j.ejim.2016.06.007 0953-6205/© 2016 Published by Elsevier B.V. on behalf of European Federation of Internal Medicine.
Please cite this article as: Giannini S, et al, Declining trends in the incidence of hip fractures in people aged 65years or over in years 2000–2011, Eur J Intern Med (2016), http://dx.doi.org/10.1016/j.ejim.2016.06.007
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S. Giannini et al. / European Journal of Internal Medicine xxx (2016) xxx–xxx
also reported an overall increase of 29.8% in the number of hip fractures during the period 2000–2009. In the same years the incidence per 10,000 inhabitants increased by 14.5% in men and 12.1% in women. Interestingly, the authors also showed that women aged 65–74 years experienced a decrease of 7.9% in hip fractures incidence between 2004 and 2009, for the first time indicating an inversion in its temporal trend in Italy, at least in this age class. Veneto is a region located in the north-east of Italy, with a population of about 5 million of inhabitants, including seven provinces, namely those of Belluno, Padova, Rovigo, Treviso, Venezia, Verona and Vicenza. The most recent demographic data (year 2011) available for this Region were virtually identical to those observed for Italy on the whole. Indeed, the aging index was 140% and the proportion of subjects aged 65+ and 85+ years was 20.0% and 2.7%, respectively, as compared to the 20.3% and 2.8% observed for the entire Italian Country [31]. In the same period, even the estimated life expectancy at birth was quite similar in the Veneto Region as compared to Italy (females, 85.2 vs. 84.6, males, 79.9 vs.79.5, respectively). Starting from the first 2000s, the Veneto Regional Health System devoted substantial efforts aimed to improve standards of care for osteoporotic patients. In particular, in year 2004, the Regional Health Authorities have appointed two Regional Centers for Osteoporosis (belonging to the Padova and Verona University Hospitals), mainly with clinical, epidemiological and advising duties. According to this, the aim of the present study was to explore hip fracture incidence in the Veneto Region of Italy in years 2000–2011. We also wanted to look at potential differences both across the seven provinces of this Region, and in comparison with national data. 2. Methods Clinical data on hip fractures for people aged 65 years or over were obtained from hospital discharge records of the Public Regional Health System. These records include information about date of admission and discharge, diagnosis, sex, age, and patients' residence. Diagnoses are coded using the International Classification of Diseases (ICD-9CM). The quality and the completeness of coding are verified monthly by an internal process in each of the Public Hospitals of the Region. Only after this process, data are registered inside the Regional Database. Hip fractures were counted by codes 820.xx and 821.1. Hospitalization records were selected only when hip fracture was the first diagnosis and when there was an initial surgical treatment performed during the same hospitalization period. Data were collected from year 2000 through 2011 and then stratified by sex, calendar year and age class as follows: 65–69, 70–74, 75–79, 80–84, 85–89, and N89 years. Data for the single provinces of Belluno, Padova, Rovigo, Treviso, Venezia, Verona and Vicenza were also obtained. Only first hip fracture cases were included for each year considered, and cases of re-hospitalizations of the same patient were excluded. In order to exclude variabilities in estimates due to inflow or outflow of patients with hip fractures, only patients resident in the Veneto Region were considered. For the calculation of incidence rates (per 10,000 inhabitants), estimates of the regional resident population size at January 1st of each of the considered years (using the same age stratification) were used, based on data provided by the Regional Institute of Statistics [32]. We estimated the raw incidence rate for fractures and the 95% confidence interval with the method described by Ulm [33]. Direct age-standardized rates were calculated using the population of the Veneto Region for year 2011, based on data provided by the Regional Institute of Statistics [32]. Poisson regression was used to estimate the effects of age, sex, province and calendar year. Accordingly, the number of events in any cell cross-classified by age A, sex S, province P and calendar year Y was assumed to be Poisson distributed with mean μASPY = exp.(α + βA + δS + γP + τ × [Y − 1999] + log[population]), where βA represents the effect of age group A, δS represents the effect of sex
S, γP represents the effect of province P, and log[population] was entered as an offset (population = denominator of incidence rate). The standard deviation of the Poisson distribution was set to σ = √Φ where Φ is the overdispersion parameter estimated as a ratio of the Pearson chi-square to its associated degrees of freedom. The results of the regression are presented as p-values, incidence rate ratio (IRR) and 95% confidence interval (95% CI). All statistical tests were twosided and the significance level was set at the 5%. Statistical analyses were conducted with SAS 9.4 for Windows. 3. Results During the study period (2000 to 2011), a total of 53,917 hospitalizations for hip fracture were observed in the whole Veneto Region in subjects aged 65 years and over. Of these, 41,903 occurred in females (77.7%) and 12,014 in males. Among women, 35,949 hip fractures (79.3%) occurred in those aged ≥ 75 years (Table 1). The figure was almost identical for men, with 77.9% (9358) of hip fractures occurring in subjects aged ≥75 years. Table 1 also reports a detail of the number of hip fracture by age class and calendar year in males and females. During the 11-year study period, the number of hip fractures in the population aged 65+ and 75+ years increased by 17.7% and 25.5% in males and by 10.6% and 18.0% in females, respectively. Taking the 65–69 year age class as referent, the incidence rate ratio (IRR) for hip fracture significantly increased, being 1.99 (95% CI 1.88–2.11) for age class 70– 74 years, 4.12 (95% CI 3.91–4.35) for 75–79 years, 8.29 (95% CI 7.87– 8,72) for 80–84 years, 10.89 (95% CI 10.33–11.47) for 85–89 years, and 22.91 (95% CI 21.75–24.13) for ≥89 years (p b 0.0001). In Fig. 1, sex-specific incidence rates per 10,000 inhabitants for age classes in patients aged 65+ years are reported. As expected, hip fracture incidence increased exponentially in both sexes. The IRR was
Table 1 Number of hip fractures in 65 years and over males and females between years 2000 and 2011 in the Veneto Region, Italy. Males Age intervals Years
65–69
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 Total
101 85 84 68 78 71 92 105 93 91 77 89 1034
70–74 147 141 137 138 138 126 118 119 145 130 139 144 1622
75–79
80–84
85–89
N89
227 188 193 221 220 214 208 173 173 197 192 204 2410
182 161 164 213 261 266 269 252 276 282 285 281 2892
176 151 141 122 97 137 125 188 199 197 238 259 2030
169 143 176 148 181 165 179 155 170 143 195 202 2026
75–79
80–84
85–89
N89
710 677 653 680 654 639 614 567 535 550 575 544 7398
586 680 736 869 997 936 939 911 1.021 921 948 919 10,463
739 701 653 596 472 493 575 686 886 833 882 858 8374
702 816 793 849 878 861 834 739 709 797 828 908 9714
Females Age intervals Years
65–69
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 Total
197 196 174 184 164 201 163 132 169 170 158 151 2059
70–74 398 379 379 337 313 313 286 259 313 308 304 306 3895
Please cite this article as: Giannini S, et al, Declining trends in the incidence of hip fractures in people aged 65years or over in years 2000–2011, Eur J Intern Med (2016), http://dx.doi.org/10.1016/j.ejim.2016.06.007
S. Giannini et al. / European Journal of Internal Medicine xxx (2016) xxx–xxx
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Fig. 2. Age-standardized hip fractures incidence rates in 65 years and over population, by sex, calendar years 2000 to 2011, in the Veneto Region, Italy. Dotted lines indicate 95% CI. Fig. 1. Sex-specific hip fracture incidence rates by age groups in the 65 years and over population, calendar years 2000 to 2011, in the Veneto Region, Italy.
higher in females as compared to males (IRR = 1.75, 95% CI 1.70–1.79, p b 0.0001). For females, the incidence rates increased from 12.8 to 279.7 for age 65–69 and ≥ 89 years, respectively. Likewise, rates per 10,000 inhabitants for males rose from 7.2 to 211.3 for age 65–69 and ≥89 years, respectively. Table 2 shows age-standardized rates of hip fracture incidence per 10,000 inhabitants across years 2000 to 2011 for the whole Veneto Region population. A decline in age-standardized hip fracture incidence during this period was observed. There was a 10% decrease by year 2004 (IRR 0.90, 95% CI 0.86–0.95). The reduction in hip fracture incidence reached its maximum by year 2007 (IRR 0.79, 95% CI 0.75–0.84) and stabilized thereafter, being 18% by year 2011 (IRR 0.82, 95% CI 0.78–0.87). All the effects considered in the Poisson model resulted statistically significant with p b 0.0001. In Fig. 2, sex-specific age-standardized hip fracture incidence rates per 10,000 inhabitants across the entire study period are reported. In females, hip fracture incidence decreased constantly up to year 2007, from 71.7 in year 2000 to 58.7 in 2007 (−18%). The lowest hip fracture incidence of 58.2 was observed by year 2011. In males, hip fracture incidence decreased across years 2000–2011, from 46.5 at the baseline to 37.5 at the end of the observation period, respectively. The maximum decline was reached by year 2009, with hip fracture incidence rate being 34.7 in this year.
Hip fractures incidence rates per 10,000 inhabitants considered according to age groups are reported in Fig. 3. There was a progressive and almost identical percent decrease in hip fracture incidence rates in age classes 65–69, 70–74, 75–79 years (− 26%, − 29% and − 28%, respectively) by year 2011 (Fig. 3a). The same trend in the percent
Table 2 Age-standardized incidence rates of hip fracture × 10,000 inhabitants in the whole 65 years and over population, calendar years 2000 to 2011, in the Veneto Region, Italy. Incidence rate ratios (IRR) and 95% CI are given. Calendar year
Age-standardized rates (95% CI)
IRR (95% CI) from Poisson regression
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011
61.13 (59.29–63.02) 59.68 (57.88–61.52) 56.68 (54.98–58.42) 56.70 (55.03–58.41) 55.06 (53.43–56.72) 52.81 (51.23–54.43) 51.43 (49.89–53.01) 49.41 (47.93–50.94) 52.25 (50.76–53.77) 50.32 (48.88–51.80) 51.48 (50.03–52.96) 50.03 (48.63–51.45)
1 (reference) 0.96 (0.91–1.02) 0.92 (0.87–0.97) 0.92 (0.87–0.97) 0.90 (0.86–0.95) 0.86 (0.81–0.91) 0.83 (0.79–0.88) 0.79 (0.75–0.84) 0.85 (0.80–0.90) 0.82 (0.78–0.87) 0.84 (0.80–0.89) 0.82 (0.78–0.87)
Fig. 3. Hip fractures incidence rates in the 65 years and over population, by age class and calendar years 2000 to 2011, in the Veneto Region, Italy. (a) Incidence rates for age classes 65–69 (circles), 70–74 (squares), and 75–79 (triangles) years are reported. (b) Incidence rates for age classes 80–84 (circles), 85–89 (squares), and N89 years (triangles) are reported.
Please cite this article as: Giannini S, et al, Declining trends in the incidence of hip fractures in people aged 65years or over in years 2000–2011, Eur J Intern Med (2016), http://dx.doi.org/10.1016/j.ejim.2016.06.007
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S. Giannini et al. / European Journal of Internal Medicine xxx (2016) xxx–xxx
Fig. 4. (a) Incidence rate ratio (95% CI) of hip fracture by province, in 65 years and over population, calendar years 2000 to 2011, in the Veneto Region, Italy, taking Vicenza province as reference. (b) Age-standardized hip fractures incidence rates by provinces (Padova plus Verona, squares vs. others, circles) and calendar years 2000 to 2011, in the Veneto Region, Italy. Dotted lines represent 95% CI.
decrease, even if less pronounced (−17%), was observed in the age class 80–84 years (Fig. 3b). However, hip fracture incidence did not show any reduction in subjects aged 85–89, while in subjects 89+ years it progressively declined by year 2007, then increasing thereafter (Fig. 3b). We also evaluated the IRR (95% CI) of age-standardized hip fractures incidence for the seven provinces of the Veneto Region, taking Vicenza province as reference (Fig. 4a). Hip fracture incidence in the whole 2000 to 2011 period of observation was significantly lower in the Padova (IRR 0.63, 95% CI 0.60–0.66, p b 0.0001) and Verona (IRR 0.66, 95% CI 0.63–0.70, p b 0.0001) provinces, while no differences were observed for the others [Belluno, 0.98 (0.92–1.05), Rovigo, 0.96 (0.90– 1.02), Treviso, 0.99 (0.94–1.03), and Venezia, 0.95 (0.90–1.00)]. Fig. 4b also depicts the trend of age-standardized hip fracture incidence rates per 10,000 inhabitants for the seven provinces belonging to the Veneto Region, across years 2000–2011. Given that the IRR and CIs were very similar for Padova and Verona across the whole study period (Fig. 4a), data cumulated for these two provinces. Provided that the same was also true for the remaining five provinces (Fig. 4a), data were also pooled together for Belluno, Rovigo, Treviso, Venezia and Vicenza. From year 2000 to 2011 there was a decrease of 22% (IRR 0.78, 95% CI 0.73–0.85, p b 0.0001) for Padova and Verona taken together and of 17% for the other provinces (IRR 0.83, 95% CI 0.79–0.88, p b 0.0001). 4. Discussion This study focused on hip fracture incidence trends in subjects aged 65 years and over, for the period 2000–2011, in the Veneto Region of Italy. This Region has a population of about 5,000,000 of inhabitants,
distributed in seven provinces, namely Belluno, Padova, Rovigo, Treviso, Venezia, Verona and Vicenza. As expected, sex-specific hip fracture incidence rate was significantly higher in women than in men. Our results also indicate that the crude number of hip fractures rose during the observation period and the increase was larger in males as compared to females and, in both sexes, in older subjects. However, when age-standardized, hip fracture rates progressively decreased during the observation period, reaching the nadir by year 2007 and remaining stable thereafter. These results are not surprising. Indeed, even if an increase in hip fracture incidence has been described in recent years for several Countries [22,34], including Italy [28–30], a decrease in hip fracture incidence in years 1980–2010 has been described in others, such as for North America [16,17,35], and Australia [10], with the fall being in the order of 15–20%. Accordingly, even in many European Countries hip fracture incidence has shown a relevant decline [6,9], or at least a tendency toward a plateau in calendar years 1995–2005 [20–25]. Several hypotheses have been proposed to explain this phenomenon. The possibility of a birth cohort effect, then resulting in a healthier aging population, is considered one of the most reliable [36,37]. The role of a period effect, that reflects changes occurring at a specific time, has been underlined by others, who found a relationship between the widespread introduction of diagnostic as well as therapeutic interventions for osteoporosis and the decline in hip fracture incidence [17,38–40]. The hypothesis of a cohort effect as a major determinant of our results seems rather unlikely for some reasons. The sharp difference between our data and those published on hip fracture incidence for Italy as a whole is one of these. Indeed, Piscitelli et al. have recently carried out a study aimed to evaluate the trend in hip fracture incidence in Italy, by analyzing the National Hospitalization Database of the Italian Ministry of Health, which is obtained by collecting data from the single regional hospitalization databases [30], like that in use in our Region. They found that, in the Italian population as a whole aged 65 years and upward, the absolute number of hip fracture increased by 27% and 36% in females and males, respectively, during the period 2000– 2009. In addition, they reported that even the incidence per 10,000 inhabitants showed an increase of 14.5% in men and 12.1% in women over the same 10-year period [30]. We also found that the crude hip fracture rate rose in the Veneto Region in the same calendar years considered in the Piscitelli's study. However, this increase was less than a half than that reported in the above-mentioned study, in a population quite comparable for age. Additionally, our age-standardized incidence rate decreased by almost 20%. None of these differences can be explained on the basis of different demographic data. Indeed, the population of the Veneto Region is quite comparable to that of the Italian Country considered as a whole. In our Region, the aging index (140%) is similar to that of Italy (147%), as well as the proportion of subjects aged 65 + (20.0 vs. 20.3%, respectively) and 85 + years (2.7 vs. 2.8%, respectively). Finally, the estimated life expectancy at birth in Veneto is 85.2 and 79.9 years for females and males, respectively, being nearly identical to the Italian demography (females, 84.6 and males, 79.5 years) [31,32]. Another finding of our study is that hip fracture incidence significantly differed among the provinces of the Veneto Region. Indeed, it was 30–35% significantly lower in the cities of Padova and Verona as compared to all the other provinces of the Veneto Region throughout the whole 2000 to 2011 period of observation. Additionally, the agestandardized hip fracture incidence rates declined more markedly in these two city areas. Again, given that the demography is quite homogeneous within the Veneto Region [32], also these results argue against a prevailing contribution of a possible cohort effect. We cannot provide any robust evidences that specific changes may have occurred in the Veneto territory to determine a welldefined period effect. However, some potential explanations should be considered. Even if there are no established evidences that a more comprehensive approach to osteoporosis management may have played a
Please cite this article as: Giannini S, et al, Declining trends in the incidence of hip fractures in people aged 65years or over in years 2000–2011, Eur J Intern Med (2016), http://dx.doi.org/10.1016/j.ejim.2016.06.007
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role [6], a relationship between the use of anti-osteoporotic drugs, a more widespread bone density testing and a decrease in hip fracture incidence have been reported by several authors [17,38–40]. The uptake of osteoporosis treatment in Italy has progressively increased in years 2001–2008, then tending to a plateau up to year 2011 [41]. A possible impact of this phenomenon on hip fracture incidence, reported for other countries [38–40], is suggested by the observation that, even in the whole Italian Country female population aged 65–74 years, a decline of 7.9% in hip fracture incidence in years 2004–2009 has been found [30]. Considering that this age group probably represents the cohort more frequently reached by anti-osteoporotic drugs, Piscitelli et al. suggested that a therapeutic intervention might have had some role [30]. Specific data for treatment uptake in the Veneto Region are not currently available. However, it could be hypothesized that a larger use of these drugs or even a more appropriate selection of patients at risk, may have been of importance. According to this, we found that hip fracture was 30–35% significantly lower in Padova and Verona as compared to all the other provinces throughout the whole 2000 to 2011 period of observation. Also, the age-standardized hip fracture incidence rates declined more markedly in these two city areas. Given that these two provinces are characterized by the presence of the two regional University Hospital Centers, it seems reasonable that a more adequate identification and management of patients at risk may have contributed to our results. A further possible contribution to a period effect to our findings, is given by the fact that, starting from the first 2000s, a community-based campaign for vitamin D supplementation was promoted by the two University Centers on a regional scale in people aged 70 years and upward [42]. This initiative was based on the well-known large prevalence of low vitamin D levels in older Italians [43] and on the results previously obtained in Verona, documenting a 10% reduction in hip fracture incidence by supplementing community-dwelling women aged 65 + years with yearly 400.000 IU vitamin D2 in the winters 2000–2001 and 2001–2002 [44]. Again, we cannot provide any data on the proportion of patients adhering to the above-mentioned regional program. However, very strong data indicate that vitamin D consumption in the Veneto region has become quite more common as compared to the rest of the country [45]. This study has some limitations. Fracture data were obtained from the administrative database of the Regional Health System and we did not perform any specific validation based on individual patient cases. Thus, we cannot completely exclude that some weakness in the registration process may have occurred. However, the quality and the completeness of coding of this database are verified monthly by an internal process in each of the Public Hospitals of the Region. Only after this process, data are registered inside the Regional Database. In addition, hip fracture cases were selected only when an initial surgical treatment was performed (and then coded) during the same hospitalization period. For these reasons, we think that the data we collected are the best possible surrogate of real hip fracture incidence in the Region. The same applies to the national data, considering that the National Registry is completely based on the regional ones, with the way of coding being the same throughout the country. Another limitation is that our database only includes hip fracture data starting from year 2000 and no information is available on previous years. Based on this, even if we excluded any second hip fracture occurring in years 2000–2011, we cannot rule out that some of the cases included are indeed second hip fractures, related to the first one occurring before year 2000. This might have contributed to a largest number of hip fractures registered in the first years of observation, partly explaining the downward trend in hip fracture incidence we observed thereafter. However, it is rather unlikely that this may have significantly affected our results. It is wellknown that the large majority of second hip fractures occur within the first 3 years after the first one [46,47,48]. This means that we may have misclassified and then overestimated the possible first hip fractures in years 2000–2002, but not later. This may have somehow contributed to the downward observed in hip fracture incidence in
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the first years of the study (2001–2002), but not in the subsequent ones, in which the same incidence reduction was observed. In addition, several studies [46,47,48] have demonstrated that the proportion of patients experiencing a second hip fracture after the first one does not exceed 7–9%. This means that, at worst, we may have overestimated the number of hip fractures of 3–4% in year 2001 and 3–4% in year 2002, while the reduction we observed at the end of the study was approximately 20%. Moreover, most of second hip fractures occur in very old subjects. This may in part explain why we did not find a clear tendency toward a reduction in hip fracture incidence in people aged 85 years or over, but not the reduction in younger cohorts of patients. Finally, the 1-year survival for second hip fractures is at least 50% less as compared to that after the first one. Again, this means that the proportion of second hip fractures cases possibly included in this study should be very low. Finally, our database does not include specific information about osteoporosis drug consumption in the Veneto Region. Thus, we cannot provide an exact measure of the impact of osteoporosis prevention and treatment on the decline in fracture incidence. Further studies on this specific issue are clearly needed. However, it is unlikely that our results may depend on the modifications in other conditions known to influence hip fracture risk. For example, the incidence of obesity is increasing in South Europe, but southern rather than northern regions of Italy seem to be more involved [49]. As far as cigarette smoking is concerned, there are not evidences demonstrating that its incidence is substantially decreasing in Italy [50]. In conclusion, we found that trends in hip fracture incidence in the Veneto Region of Italy show a relevant decline in the 2000–2011 period of observation. Even if we cannot provide reliable data on the factors responsible for this, it seems unlikely that a cohort effect may have played a prevailing role in determining our results. Further studies aimed to give more detailed information on possible cause–effect relationships are warranted.
Compliance with ethical standards Conflict of interest Sandro Giannini, Stefania Sella, Maurizio Rossini, Daniela Braghin, Davide Gatti, Maria Teresa Vilei, Annalisa Amabile, Maria Fusaro, Anna Chiara Frigo, Giuseppe Sergi, Roberto Lovato, Martino Nobile, Fabrizio Fabris and Silvano Adami declare that they have no conflict of interest.
Ethical approval All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/ or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study formal consent is not required.
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Please cite this article as: Giannini S, et al, Declining trends in the incidence of hip fractures in people aged 65years or over in years 2000–2011, Eur J Intern Med (2016), http://dx.doi.org/10.1016/j.ejim.2016.06.007
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Please cite this article as: Giannini S, et al, Declining trends in the incidence of hip fractures in people aged 65years or over in years 2000–2011, Eur J Intern Med (2016), http://dx.doi.org/10.1016/j.ejim.2016.06.007
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Original article
Declining trends in the incidence of hip fractures in people aged 65 years or over in years 2000–2011 Sandro Giannini a,⁎, Stefania Sella a, Maurizio Rossini b, Daniela Braghin a, Davide Gatti b, Maria Teresa Vilei a, Annalisa Amabile a, Maria Fusaro c, Anna Chiara Frigo d, Giuseppe Sergi e, Roberto Lovato f, Martino Nobile a, Fabrizio Fabris a, Silvano Adami b a
Clinica Medica 1, Department of Medicine, University of Padova and Regional Center for Osteoporosis, Padova, Italy Rheumatology Unit, Department of Medicine, University of Verona and Regional Center for Osteoporosis, Verona, Italy c Institute of Clinical Physiology, National Council of Research, Pisa, Italy d Department of Cardiac, Thoracic and Vascular Sciences, University of Padova, Italy e Geriatrics Division, Department of Medicine, University of Padova, Italy f Osteoporosis Center, Casa di Cura Villa Berica, Vicenza, Italy b
a r t i c l e
i n f o
Article history: Received 22 March 2016 Received in revised form 27 May 2016 Accepted 7 June 2016 Available online xxxx Keywords: Hip fracture incidence Hospitalization Osteoporosis Aging
a b s t r a c t Background: The aim of this study was to explore hip fracture (HFx) incidence in the Veneto Region of Italy, looking at potential differences with the national data. Methods: We analyzed HFx incidence for people aged 65 years or over, in years 2000–2011, using data from the Regional Hospitalization Database. Patients were stratified by sex, calendar year and 5-year age class. Data for the single provinces of the Region were also obtained. Absolute number of HFx, crude incidence for 10,000 inhabitants and age-standardized fracture rates were calculated. Results: During the study period, there were 53,917 hospitalizations for HFx (77.7% in females). In the whole 11 year period of observation, the absolute HFx number increased by 17.7% in males and 10.6% females, respectively. However, age-standardized incidence rates declined by 18% in the same period (IRR 0.82, 95% CI 0.78– 0.87). This decreasing trend was almost identical through all the age-cohorts up to 84 years. In the whole study period, HFx incidence was lower for Padova (IRR 0.63, 95% CI 0.60–0.66) and Verona (IRR 0.66, 95% CI 0.63–0.70) provinces as compared to the others. This regional profile was quite different with respect to the data published, for the same calendar years, for Italy as a whole, in spite of an almost identical demography of the population. Conclusions: HFx incidence is declining in the Veneto Region of Italy. Further studies, aimed to investigate factors involved in this figure are needed. © 2016 Published by Elsevier B.V. on behalf of European Federation of Internal Medicine.
1. Introduction Osteoporosis and related fractures are very common in the elderly and represent one of the most important causes of morbidity and mortality [1–3]. In year 2010, 3.5 million new fragility fractures were sustained in the EU countries, comprising 620,000 hip fractures, with an economic burden estimated at €37 billion [4,5]. In recent years, several studies have been carried out to investigate current trends in hip fracture incidence. While some of these studies have reported a substantial leveling-off or even a decrease in age-adjusted incidence of hip fractures [6–20], a further trend toward an increase has been described ⁎ Corresponding author at: Clinica Medica 1, Department of Medicine, Regional Center for Osteoporosis, University Hospital of Padova, Via Giustiniani, 2, 35128 Padova, Italy. Tel.: +39 049 8212169; fax: +39 049 8214459. E-mail address: [email protected] (S. Giannini).
by others [21–30]. In addition, such opposite trends have been observed in countries of the same region of the world or even within the same nation [23–25]. No definite explanations have been provided for such contrasting evidences, but different cohort or period effects could be involved [17]. According to year 2011 demographic data, Italy ranks second among European Countries for the aging index, that is a composite demographic ratio defined as the percentage between the old age population (over 65) and the young population (under 15), falling just behind Germany (147% and 154%, respectively) [31]. Due to the increasing bone fragility induced by age, a rise in hip fractures should be expected. Trends in hip fracture have been explored in Italy for the period 1999–2009 [21,26–30]. In year 2005, 94,471 patients aged 65 + years were hospitalized due to hip fractures in Italy, with an increase of 28.5% as compared to year 2000 [29]. In the same period, hospitalization costs increased by 36.1%, reaching 467 million euros in 2005. More recently, Piscitelli et al. [30]
http://dx.doi.org/10.1016/j.ejim.2016.06.007 0953-6205/© 2016 Published by Elsevier B.V. on behalf of European Federation of Internal Medicine.
Please cite this article as: Giannini S, et al, Declining trends in the incidence of hip fractures in people aged 65years or over in years 2000–2011, Eur J Intern Med (2016), http://dx.doi.org/10.1016/j.ejim.2016.06.007
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also reported an overall increase of 29.8% in the number of hip fractures during the period 2000–2009. In the same years the incidence per 10,000 inhabitants increased by 14.5% in men and 12.1% in women. Interestingly, the authors also showed that women aged 65–74 years experienced a decrease of 7.9% in hip fractures incidence between 2004 and 2009, for the first time indicating an inversion in its temporal trend in Italy, at least in this age class. Veneto is a region located in the north-east of Italy, with a population of about 5 million of inhabitants, including seven provinces, namely those of Belluno, Padova, Rovigo, Treviso, Venezia, Verona and Vicenza. The most recent demographic data (year 2011) available for this Region were virtually identical to those observed for Italy on the whole. Indeed, the aging index was 140% and the proportion of subjects aged 65+ and 85+ years was 20.0% and 2.7%, respectively, as compared to the 20.3% and 2.8% observed for the entire Italian Country [31]. In the same period, even the estimated life expectancy at birth was quite similar in the Veneto Region as compared to Italy (females, 85.2 vs. 84.6, males, 79.9 vs.79.5, respectively). Starting from the first 2000s, the Veneto Regional Health System devoted substantial efforts aimed to improve standards of care for osteoporotic patients. In particular, in year 2004, the Regional Health Authorities have appointed two Regional Centers for Osteoporosis (belonging to the Padova and Verona University Hospitals), mainly with clinical, epidemiological and advising duties. According to this, the aim of the present study was to explore hip fracture incidence in the Veneto Region of Italy in years 2000–2011. We also wanted to look at potential differences both across the seven provinces of this Region, and in comparison with national data. 2. Methods Clinical data on hip fractures for people aged 65 years or over were obtained from hospital discharge records of the Public Regional Health System. These records include information about date of admission and discharge, diagnosis, sex, age, and patients' residence. Diagnoses are coded using the International Classification of Diseases (ICD-9CM). The quality and the completeness of coding are verified monthly by an internal process in each of the Public Hospitals of the Region. Only after this process, data are registered inside the Regional Database. Hip fractures were counted by codes 820.xx and 821.1. Hospitalization records were selected only when hip fracture was the first diagnosis and when there was an initial surgical treatment performed during the same hospitalization period. Data were collected from year 2000 through 2011 and then stratified by sex, calendar year and age class as follows: 65–69, 70–74, 75–79, 80–84, 85–89, and N89 years. Data for the single provinces of Belluno, Padova, Rovigo, Treviso, Venezia, Verona and Vicenza were also obtained. Only first hip fracture cases were included for each year considered, and cases of re-hospitalizations of the same patient were excluded. In order to exclude variabilities in estimates due to inflow or outflow of patients with hip fractures, only patients resident in the Veneto Region were considered. For the calculation of incidence rates (per 10,000 inhabitants), estimates of the regional resident population size at January 1st of each of the considered years (using the same age stratification) were used, based on data provided by the Regional Institute of Statistics [32]. We estimated the raw incidence rate for fractures and the 95% confidence interval with the method described by Ulm [33]. Direct age-standardized rates were calculated using the population of the Veneto Region for year 2011, based on data provided by the Regional Institute of Statistics [32]. Poisson regression was used to estimate the effects of age, sex, province and calendar year. Accordingly, the number of events in any cell cross-classified by age A, sex S, province P and calendar year Y was assumed to be Poisson distributed with mean μASPY = exp.(α + βA + δS + γP + τ × [Y − 1999] + log[population]), where βA represents the effect of age group A, δS represents the effect of sex
S, γP represents the effect of province P, and log[population] was entered as an offset (population = denominator of incidence rate). The standard deviation of the Poisson distribution was set to σ = √Φ where Φ is the overdispersion parameter estimated as a ratio of the Pearson chi-square to its associated degrees of freedom. The results of the regression are presented as p-values, incidence rate ratio (IRR) and 95% confidence interval (95% CI). All statistical tests were twosided and the significance level was set at the 5%. Statistical analyses were conducted with SAS 9.4 for Windows. 3. Results During the study period (2000 to 2011), a total of 53,917 hospitalizations for hip fracture were observed in the whole Veneto Region in subjects aged 65 years and over. Of these, 41,903 occurred in females (77.7%) and 12,014 in males. Among women, 35,949 hip fractures (79.3%) occurred in those aged ≥ 75 years (Table 1). The figure was almost identical for men, with 77.9% (9358) of hip fractures occurring in subjects aged ≥75 years. Table 1 also reports a detail of the number of hip fracture by age class and calendar year in males and females. During the 11-year study period, the number of hip fractures in the population aged 65+ and 75+ years increased by 17.7% and 25.5% in males and by 10.6% and 18.0% in females, respectively. Taking the 65–69 year age class as referent, the incidence rate ratio (IRR) for hip fracture significantly increased, being 1.99 (95% CI 1.88–2.11) for age class 70– 74 years, 4.12 (95% CI 3.91–4.35) for 75–79 years, 8.29 (95% CI 7.87– 8,72) for 80–84 years, 10.89 (95% CI 10.33–11.47) for 85–89 years, and 22.91 (95% CI 21.75–24.13) for ≥89 years (p b 0.0001). In Fig. 1, sex-specific incidence rates per 10,000 inhabitants for age classes in patients aged 65+ years are reported. As expected, hip fracture incidence increased exponentially in both sexes. The IRR was
Table 1 Number of hip fractures in 65 years and over males and females between years 2000 and 2011 in the Veneto Region, Italy. Males Age intervals Years
65–69
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 Total
101 85 84 68 78 71 92 105 93 91 77 89 1034
70–74 147 141 137 138 138 126 118 119 145 130 139 144 1622
75–79
80–84
85–89
N89
227 188 193 221 220 214 208 173 173 197 192 204 2410
182 161 164 213 261 266 269 252 276 282 285 281 2892
176 151 141 122 97 137 125 188 199 197 238 259 2030
169 143 176 148 181 165 179 155 170 143 195 202 2026
75–79
80–84
85–89
N89
710 677 653 680 654 639 614 567 535 550 575 544 7398
586 680 736 869 997 936 939 911 1.021 921 948 919 10,463
739 701 653 596 472 493 575 686 886 833 882 858 8374
702 816 793 849 878 861 834 739 709 797 828 908 9714
Females Age intervals Years
65–69
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 Total
197 196 174 184 164 201 163 132 169 170 158 151 2059
70–74 398 379 379 337 313 313 286 259 313 308 304 306 3895
Please cite this article as: Giannini S, et al, Declining trends in the incidence of hip fractures in people aged 65years or over in years 2000–2011, Eur J Intern Med (2016), http://dx.doi.org/10.1016/j.ejim.2016.06.007
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Fig. 2. Age-standardized hip fractures incidence rates in 65 years and over population, by sex, calendar years 2000 to 2011, in the Veneto Region, Italy. Dotted lines indicate 95% CI. Fig. 1. Sex-specific hip fracture incidence rates by age groups in the 65 years and over population, calendar years 2000 to 2011, in the Veneto Region, Italy.
higher in females as compared to males (IRR = 1.75, 95% CI 1.70–1.79, p b 0.0001). For females, the incidence rates increased from 12.8 to 279.7 for age 65–69 and ≥ 89 years, respectively. Likewise, rates per 10,000 inhabitants for males rose from 7.2 to 211.3 for age 65–69 and ≥89 years, respectively. Table 2 shows age-standardized rates of hip fracture incidence per 10,000 inhabitants across years 2000 to 2011 for the whole Veneto Region population. A decline in age-standardized hip fracture incidence during this period was observed. There was a 10% decrease by year 2004 (IRR 0.90, 95% CI 0.86–0.95). The reduction in hip fracture incidence reached its maximum by year 2007 (IRR 0.79, 95% CI 0.75–0.84) and stabilized thereafter, being 18% by year 2011 (IRR 0.82, 95% CI 0.78–0.87). All the effects considered in the Poisson model resulted statistically significant with p b 0.0001. In Fig. 2, sex-specific age-standardized hip fracture incidence rates per 10,000 inhabitants across the entire study period are reported. In females, hip fracture incidence decreased constantly up to year 2007, from 71.7 in year 2000 to 58.7 in 2007 (−18%). The lowest hip fracture incidence of 58.2 was observed by year 2011. In males, hip fracture incidence decreased across years 2000–2011, from 46.5 at the baseline to 37.5 at the end of the observation period, respectively. The maximum decline was reached by year 2009, with hip fracture incidence rate being 34.7 in this year.
Hip fractures incidence rates per 10,000 inhabitants considered according to age groups are reported in Fig. 3. There was a progressive and almost identical percent decrease in hip fracture incidence rates in age classes 65–69, 70–74, 75–79 years (− 26%, − 29% and − 28%, respectively) by year 2011 (Fig. 3a). The same trend in the percent
Table 2 Age-standardized incidence rates of hip fracture × 10,000 inhabitants in the whole 65 years and over population, calendar years 2000 to 2011, in the Veneto Region, Italy. Incidence rate ratios (IRR) and 95% CI are given. Calendar year
Age-standardized rates (95% CI)
IRR (95% CI) from Poisson regression
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011
61.13 (59.29–63.02) 59.68 (57.88–61.52) 56.68 (54.98–58.42) 56.70 (55.03–58.41) 55.06 (53.43–56.72) 52.81 (51.23–54.43) 51.43 (49.89–53.01) 49.41 (47.93–50.94) 52.25 (50.76–53.77) 50.32 (48.88–51.80) 51.48 (50.03–52.96) 50.03 (48.63–51.45)
1 (reference) 0.96 (0.91–1.02) 0.92 (0.87–0.97) 0.92 (0.87–0.97) 0.90 (0.86–0.95) 0.86 (0.81–0.91) 0.83 (0.79–0.88) 0.79 (0.75–0.84) 0.85 (0.80–0.90) 0.82 (0.78–0.87) 0.84 (0.80–0.89) 0.82 (0.78–0.87)
Fig. 3. Hip fractures incidence rates in the 65 years and over population, by age class and calendar years 2000 to 2011, in the Veneto Region, Italy. (a) Incidence rates for age classes 65–69 (circles), 70–74 (squares), and 75–79 (triangles) years are reported. (b) Incidence rates for age classes 80–84 (circles), 85–89 (squares), and N89 years (triangles) are reported.
Please cite this article as: Giannini S, et al, Declining trends in the incidence of hip fractures in people aged 65years or over in years 2000–2011, Eur J Intern Med (2016), http://dx.doi.org/10.1016/j.ejim.2016.06.007
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Fig. 4. (a) Incidence rate ratio (95% CI) of hip fracture by province, in 65 years and over population, calendar years 2000 to 2011, in the Veneto Region, Italy, taking Vicenza province as reference. (b) Age-standardized hip fractures incidence rates by provinces (Padova plus Verona, squares vs. others, circles) and calendar years 2000 to 2011, in the Veneto Region, Italy. Dotted lines represent 95% CI.
decrease, even if less pronounced (−17%), was observed in the age class 80–84 years (Fig. 3b). However, hip fracture incidence did not show any reduction in subjects aged 85–89, while in subjects 89+ years it progressively declined by year 2007, then increasing thereafter (Fig. 3b). We also evaluated the IRR (95% CI) of age-standardized hip fractures incidence for the seven provinces of the Veneto Region, taking Vicenza province as reference (Fig. 4a). Hip fracture incidence in the whole 2000 to 2011 period of observation was significantly lower in the Padova (IRR 0.63, 95% CI 0.60–0.66, p b 0.0001) and Verona (IRR 0.66, 95% CI 0.63–0.70, p b 0.0001) provinces, while no differences were observed for the others [Belluno, 0.98 (0.92–1.05), Rovigo, 0.96 (0.90– 1.02), Treviso, 0.99 (0.94–1.03), and Venezia, 0.95 (0.90–1.00)]. Fig. 4b also depicts the trend of age-standardized hip fracture incidence rates per 10,000 inhabitants for the seven provinces belonging to the Veneto Region, across years 2000–2011. Given that the IRR and CIs were very similar for Padova and Verona across the whole study period (Fig. 4a), data cumulated for these two provinces. Provided that the same was also true for the remaining five provinces (Fig. 4a), data were also pooled together for Belluno, Rovigo, Treviso, Venezia and Vicenza. From year 2000 to 2011 there was a decrease of 22% (IRR 0.78, 95% CI 0.73–0.85, p b 0.0001) for Padova and Verona taken together and of 17% for the other provinces (IRR 0.83, 95% CI 0.79–0.88, p b 0.0001). 4. Discussion This study focused on hip fracture incidence trends in subjects aged 65 years and over, for the period 2000–2011, in the Veneto Region of Italy. This Region has a population of about 5,000,000 of inhabitants,
distributed in seven provinces, namely Belluno, Padova, Rovigo, Treviso, Venezia, Verona and Vicenza. As expected, sex-specific hip fracture incidence rate was significantly higher in women than in men. Our results also indicate that the crude number of hip fractures rose during the observation period and the increase was larger in males as compared to females and, in both sexes, in older subjects. However, when age-standardized, hip fracture rates progressively decreased during the observation period, reaching the nadir by year 2007 and remaining stable thereafter. These results are not surprising. Indeed, even if an increase in hip fracture incidence has been described in recent years for several Countries [22,34], including Italy [28–30], a decrease in hip fracture incidence in years 1980–2010 has been described in others, such as for North America [16,17,35], and Australia [10], with the fall being in the order of 15–20%. Accordingly, even in many European Countries hip fracture incidence has shown a relevant decline [6,9], or at least a tendency toward a plateau in calendar years 1995–2005 [20–25]. Several hypotheses have been proposed to explain this phenomenon. The possibility of a birth cohort effect, then resulting in a healthier aging population, is considered one of the most reliable [36,37]. The role of a period effect, that reflects changes occurring at a specific time, has been underlined by others, who found a relationship between the widespread introduction of diagnostic as well as therapeutic interventions for osteoporosis and the decline in hip fracture incidence [17,38–40]. The hypothesis of a cohort effect as a major determinant of our results seems rather unlikely for some reasons. The sharp difference between our data and those published on hip fracture incidence for Italy as a whole is one of these. Indeed, Piscitelli et al. have recently carried out a study aimed to evaluate the trend in hip fracture incidence in Italy, by analyzing the National Hospitalization Database of the Italian Ministry of Health, which is obtained by collecting data from the single regional hospitalization databases [30], like that in use in our Region. They found that, in the Italian population as a whole aged 65 years and upward, the absolute number of hip fracture increased by 27% and 36% in females and males, respectively, during the period 2000– 2009. In addition, they reported that even the incidence per 10,000 inhabitants showed an increase of 14.5% in men and 12.1% in women over the same 10-year period [30]. We also found that the crude hip fracture rate rose in the Veneto Region in the same calendar years considered in the Piscitelli's study. However, this increase was less than a half than that reported in the above-mentioned study, in a population quite comparable for age. Additionally, our age-standardized incidence rate decreased by almost 20%. None of these differences can be explained on the basis of different demographic data. Indeed, the population of the Veneto Region is quite comparable to that of the Italian Country considered as a whole. In our Region, the aging index (140%) is similar to that of Italy (147%), as well as the proportion of subjects aged 65 + (20.0 vs. 20.3%, respectively) and 85 + years (2.7 vs. 2.8%, respectively). Finally, the estimated life expectancy at birth in Veneto is 85.2 and 79.9 years for females and males, respectively, being nearly identical to the Italian demography (females, 84.6 and males, 79.5 years) [31,32]. Another finding of our study is that hip fracture incidence significantly differed among the provinces of the Veneto Region. Indeed, it was 30–35% significantly lower in the cities of Padova and Verona as compared to all the other provinces of the Veneto Region throughout the whole 2000 to 2011 period of observation. Additionally, the agestandardized hip fracture incidence rates declined more markedly in these two city areas. Again, given that the demography is quite homogeneous within the Veneto Region [32], also these results argue against a prevailing contribution of a possible cohort effect. We cannot provide any robust evidences that specific changes may have occurred in the Veneto territory to determine a welldefined period effect. However, some potential explanations should be considered. Even if there are no established evidences that a more comprehensive approach to osteoporosis management may have played a
Please cite this article as: Giannini S, et al, Declining trends in the incidence of hip fractures in people aged 65years or over in years 2000–2011, Eur J Intern Med (2016), http://dx.doi.org/10.1016/j.ejim.2016.06.007
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role [6], a relationship between the use of anti-osteoporotic drugs, a more widespread bone density testing and a decrease in hip fracture incidence have been reported by several authors [17,38–40]. The uptake of osteoporosis treatment in Italy has progressively increased in years 2001–2008, then tending to a plateau up to year 2011 [41]. A possible impact of this phenomenon on hip fracture incidence, reported for other countries [38–40], is suggested by the observation that, even in the whole Italian Country female population aged 65–74 years, a decline of 7.9% in hip fracture incidence in years 2004–2009 has been found [30]. Considering that this age group probably represents the cohort more frequently reached by anti-osteoporotic drugs, Piscitelli et al. suggested that a therapeutic intervention might have had some role [30]. Specific data for treatment uptake in the Veneto Region are not currently available. However, it could be hypothesized that a larger use of these drugs or even a more appropriate selection of patients at risk, may have been of importance. According to this, we found that hip fracture was 30–35% significantly lower in Padova and Verona as compared to all the other provinces throughout the whole 2000 to 2011 period of observation. Also, the age-standardized hip fracture incidence rates declined more markedly in these two city areas. Given that these two provinces are characterized by the presence of the two regional University Hospital Centers, it seems reasonable that a more adequate identification and management of patients at risk may have contributed to our results. A further possible contribution to a period effect to our findings, is given by the fact that, starting from the first 2000s, a community-based campaign for vitamin D supplementation was promoted by the two University Centers on a regional scale in people aged 70 years and upward [42]. This initiative was based on the well-known large prevalence of low vitamin D levels in older Italians [43] and on the results previously obtained in Verona, documenting a 10% reduction in hip fracture incidence by supplementing community-dwelling women aged 65 + years with yearly 400.000 IU vitamin D2 in the winters 2000–2001 and 2001–2002 [44]. Again, we cannot provide any data on the proportion of patients adhering to the above-mentioned regional program. However, very strong data indicate that vitamin D consumption in the Veneto region has become quite more common as compared to the rest of the country [45]. This study has some limitations. Fracture data were obtained from the administrative database of the Regional Health System and we did not perform any specific validation based on individual patient cases. Thus, we cannot completely exclude that some weakness in the registration process may have occurred. However, the quality and the completeness of coding of this database are verified monthly by an internal process in each of the Public Hospitals of the Region. Only after this process, data are registered inside the Regional Database. In addition, hip fracture cases were selected only when an initial surgical treatment was performed (and then coded) during the same hospitalization period. For these reasons, we think that the data we collected are the best possible surrogate of real hip fracture incidence in the Region. The same applies to the national data, considering that the National Registry is completely based on the regional ones, with the way of coding being the same throughout the country. Another limitation is that our database only includes hip fracture data starting from year 2000 and no information is available on previous years. Based on this, even if we excluded any second hip fracture occurring in years 2000–2011, we cannot rule out that some of the cases included are indeed second hip fractures, related to the first one occurring before year 2000. This might have contributed to a largest number of hip fractures registered in the first years of observation, partly explaining the downward trend in hip fracture incidence we observed thereafter. However, it is rather unlikely that this may have significantly affected our results. It is wellknown that the large majority of second hip fractures occur within the first 3 years after the first one [46,47,48]. This means that we may have misclassified and then overestimated the possible first hip fractures in years 2000–2002, but not later. This may have somehow contributed to the downward observed in hip fracture incidence in
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the first years of the study (2001–2002), but not in the subsequent ones, in which the same incidence reduction was observed. In addition, several studies [46,47,48] have demonstrated that the proportion of patients experiencing a second hip fracture after the first one does not exceed 7–9%. This means that, at worst, we may have overestimated the number of hip fractures of 3–4% in year 2001 and 3–4% in year 2002, while the reduction we observed at the end of the study was approximately 20%. Moreover, most of second hip fractures occur in very old subjects. This may in part explain why we did not find a clear tendency toward a reduction in hip fracture incidence in people aged 85 years or over, but not the reduction in younger cohorts of patients. Finally, the 1-year survival for second hip fractures is at least 50% less as compared to that after the first one. Again, this means that the proportion of second hip fractures cases possibly included in this study should be very low. Finally, our database does not include specific information about osteoporosis drug consumption in the Veneto Region. Thus, we cannot provide an exact measure of the impact of osteoporosis prevention and treatment on the decline in fracture incidence. Further studies on this specific issue are clearly needed. However, it is unlikely that our results may depend on the modifications in other conditions known to influence hip fracture risk. For example, the incidence of obesity is increasing in South Europe, but southern rather than northern regions of Italy seem to be more involved [49]. As far as cigarette smoking is concerned, there are not evidences demonstrating that its incidence is substantially decreasing in Italy [50]. In conclusion, we found that trends in hip fracture incidence in the Veneto Region of Italy show a relevant decline in the 2000–2011 period of observation. Even if we cannot provide reliable data on the factors responsible for this, it seems unlikely that a cohort effect may have played a prevailing role in determining our results. Further studies aimed to give more detailed information on possible cause–effect relationships are warranted.
Compliance with ethical standards Conflict of interest Sandro Giannini, Stefania Sella, Maurizio Rossini, Daniela Braghin, Davide Gatti, Maria Teresa Vilei, Annalisa Amabile, Maria Fusaro, Anna Chiara Frigo, Giuseppe Sergi, Roberto Lovato, Martino Nobile, Fabrizio Fabris and Silvano Adami declare that they have no conflict of interest.
Ethical approval All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/ or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study formal consent is not required.
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Please cite this article as: Giannini S, et al, Declining trends in the incidence of hip fractures in people aged 65years or over in years 2000–2011, Eur J Intern Med (2016), http://dx.doi.org/10.1016/j.ejim.2016.06.007