The Fracture Liaison Service of the Virgen Macarena University Hospital Reduces the Gap in the Management of Osteoporosis, Particularly in Men. It Meets the International Osteoporosis Foundation Quality Standards

Journal of Clinical Medicine Article The Fracture Liaison Service of the Virgen Macarena University Hospital Reduces the Gap in the Management of Osteoporosis, Particularly in Men. It Meets the International Osteoporosis Foundation Quality Standards Francisco-Jesús Olmo-Montes 1, Blanca Hernández-Cruz 2,* , Mª JoséMiranda 1, Mª Dolores Jimenez-Moreno 1, Mª Ángeles Vázquez-Gámez 3, MercèGiner 3, Miguel-Angel Colmenero 1, JoséJavier Pérez-Venegas 2 and María-JoséMontoya-García3   Citation: Olmo-Montes, F.-J.; Hernández-Cruz, B.; Miranda, M.J.; Jimenez-Moreno, M.D.; Vázquez-Gámez, M.Á.; Giner, M.; Colmenero, M.-A.; Pérez-Venegas, J.J.; Montoya-García, M.-J. The Fracture Liaison Service of the Virgen Macarena University Hospital Reduces the Gap in the Management of Osteoporosis, Particularly in Men. It Meets the International Osteoporosis Foundation Quality Standards. J. Clin. Med. 2021,10, 4220. https://doi.org/10.3390/ jcm10184220 Academic Editors: Umberto Tarantino, Heinrich Resch and Jorge A. Roman-Blas Received: 18 July 2021 Accepted: 15 September 2021 Published: 17 September 2021 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). 1Internal Medicine Department, Virgen Macarena University Hospital, Dr Fedriani Avenue No 3, 41009 Seville, Spain; [email protected] (F.-J.O.-M.); [email protected] (M.J.M.); [email protected] (M.D.J.-M.); [email protected] (M.-A.C.) 2Rheumatology Department, Virgen Macarena University Hospital, Dr Fedriani Avenue No 3, 41009 Seville, Spain; [email protected] 3PAIDI Research Group CTS/211, Medicine Department, School of Medicine, Seville University, Sanchez Pizjuan SN, 41009 Seville, Spain; [email protected] (M.Á.V.-G.); mer[email protected] (M.G.); [email protected] (M.-J.M.-G.) *Correspondence: [email protected]; Tel.: +34-954-78-22-06 Abstract: Objectives: To describe the Fracture Liaison Service (FLS), to know the characteristics of the patients attended with emphasis on sex differences, and to know the compliance of International Osteoporosis Foundation (IOF) quality standards. Methods: Observational, prospective research. All the consecutive patients that attended in usual clinical practice from May 2018 to October 2019, were over 50 years, and with a fragility fracture (FF), were included. Results: Our FLS is a type A multidisciplinary unit. We included 410 patients, 80% women. FF recorded in 328 women were: Hip (132, 40%), Clinical Vertebral (81, 25%) and No hip No vertebral (115, 35%). Those in 82 men were: Hip (53, 66%), Clinical Vertebral (20, 24%) and No hip No vertebral (9, 10%), p= 0.0001. Men had more secondary osteoporosis (OP). The most remarkable result was the low percentage of patients with OP receiving treatment and the differences between sex. Forty-nine (16%) women versus nine (7%) men had received it at some point in their lives, p= 0.04. The probability of a man not receiving prior treatment was 2.5 (95%CI 1.01–6.51); p= 0.04, and after the FF was 0.64 (0.38–1.09). Treatment adherence in the first year after the FLS was 96% in both sexes. The completion of IOF quality standards was bad for patient identification and reference time. It was poor for initial OP screening standard and good for the remaining ten indicators. Conclusions: the FLS narrowed the gap in diagnosis, treatment, and follow-up of fragility fracture patients, especially men. The FLS meets the IOF quality standards. Keywords: osteoporosis treatment; quality standards; fracture liaison service type a; gender disparities in OP 1. Introduction Osteoporosis (OP) is a global public health problem [ 1 – 3 ]. It causes 8.9 million fractures annually worldwide. It is estimated that 1000 bone fragility fractures (FF) occur every hour. The probability of having a major FF from the age of 50 for the rest of life is 46% in women and 22% in men [ 1 ]. Spain is a country with a mean incidence of OP, with 150 to 250 new cases a year per 100,000 adults over 50 years [1,2]. In recent years, there have been advances in the management of patients with OP. Highlights include tools for estimating fracture risk, effective and safe treatments [ 1 – 3 ], J. Clin. Med. 2021,10, 4220. https://doi.org/10.3390/jcm10184220 https://www.mdpi.com/journal/jcm J. Clin. Med. 2021,10, 4220 2 of 17 and incorporating the “Treat to Target” strategy into the disease [ 4 ]. Despite this, a gap between OP recommendations and clinical practice continues to be identified [ 1 – 3 ]. This large gap occurs in: (i) Identifying cases, (ii) Diagnostic, (iii) Estimating the risk of FF and falls, (iv) Treatment, and (v) Therapeutic adherence [ 1 – 3 ]. As an example, after the first hip, 80% of patients do not receive evaluation and/or OP treatment in the following year [ 1 – 3 ]. This gap is worse among men [2]. Another overwhelming fact was the decline in the bisphosphonates treatment rate of patients with a hip FF in the United States that happened between 2002 and 2011. That was a drop from 40% to 20%, in the year after the discharge [ 5 ]. In these patients the risk of non-treatment among men versus women was 54% higher, p< 0.0001 [ 5 ]. For most Immune-Mediated Diseases the gender minority falls to women. Among all the patients with OP the worst assessed, diagnosed, and treated are men [ 2 , 5 , 6 ]. In addition, men have higher rates of secondary OP and a greater treatment gap [ 5 , 6 ]. Over the past 20 years, men have seen an increase in the incidence of FF, particularly in those over 75 years and with hip fractures. In women, the tendency of the FF is to decrease [7]. To narrow the gap and to improve the diagnosis and treatment of patients with OP, Fracture Liaison Services (FLS) were created. The first FLS appeared in the late 1990s in Glasgow, United Kingdom [ 8 ]. Subsequently, the “National Institute for Health and Care Excellence” approved its efficiency [ 9 ]. Over the years, the FLSs have been consolidated and spread throughout the world as an initiative of the International Osteoporosis Foundation (IOF) [ 10 ] and the American Society for Bone and Mineral Research (ASBMR) [ 11 ]. In 2017, the European League against Rheumatisms (EULAR) and the European Federation of National Associations of Orthopaedics and Traumatology (ESCEO) joined the initiative [ 12 ]. There are currently more than 300 FLSs spread around the world. They work with different models, adapted to the circumstances of each country and health system [1–3,8–16] . A great heterogeneity is recognised in the different FLS models [ 12 – 14 ]. To consolidate these models, Ganda et al. proposed to classify them according to the intensity of the intervention [ 15 ], A: There is a coordinator in charge of high intensity or type A. For these, after the first FF the patient is captured, evaluated, and diagnosed. Plans of follow-up and treatment are established together with primary care (PC). B: Type B can have a coordinator, the patient is received and evaluated, and the treatment and follow-up plans are carried out by the PC physician, preferably in conjunction with the FLS. C: In type C, the patient is received and assessed in the FLS. An estimate of the risk of FF is made and recommendations are issued, keeping the patient informed. In this case, the patient care is delegated to the PC physician and the intervention is of lower intensity. D: The type D is the least intensive. It informs the patient, but no evaluation is carried out and follow-up is done by the PC physician, with whom there is no communication [8–16]. European guides recommend the FLSs as the secondary prevention standard for FF, although some perform primary prevention [ 1 – 3 , 8 – 16 ]. The ones that work best are those of Type A, in which the risk of FF and falls is estimated, and the therapeutic strategy is shared with PC and are multidisciplinary. That means there is a coordinator who organises orthopaedic surgery and traumatology, rehabilitation, rheumatology, and “fall prevention services” [ 8 – 15 ]. Regardless of which FLS model is implemented, the IOF, and the National Osteoporosis Foundation (NOF) set the quality standards that they must meet [8–15]. These standards called “The Best Practice Framework” have already been published [13–15] . A standard compliant FLS has demonstrated numerous benefits. Reducing between 15% and 30% in re-fracture rates. Reduction in hip fracture mortality after the first month of 0.73 (CI95% 0.65–0.82); and after the first year of 0.81 (0.75–0.87) [ 17 ]. Besides, a significant increased risk estimation of FF, falls and evaluation of secondary causes of OP, lead to an increase of prescription from 15% to 40% [ 8 – 16 ]. The Virgen Macarena University Hospital (VMUH) transformed its FLS (VMUH-FLS) in May 2018 into a multidisciplinary unit, with improved communication with PC [ 18 ]. We decided to make an initial evaluation after 18 months of operation. The aims of the study were: (i) To describe the characteristics of the FLS and how it works, (ii) To know the type of patients J. Clin. Med. 2021,10, 4220 3 of 17 being treated, with an emphasis on gender differences, and (iii) To know the degree of completion of The Best Practice Framework quality standards according to IOF. 2. Materials and Methods 2.1. Study Design This study was a a prospective, observational, and analytical one in regular clinical practice. It took place from 1st May 2018, to 31st October 2019. Setting: VMUH is an 850 bed , teaching hospital, serving a population of approximately 481,296 inhabitants (157,428 over 50 years old) in Seville, Spain. This population can be treated in 34 PC health areas [ 18 ]. The VMUH belongs to the Public Health System of Andalusia, with universal coverage for medical consultation, laboratory tests, X-Ray films, bone densitometry test (BMD). It also covers all specific treatments for OP. All candidate patients are valued for inclusion in VMUH-FLS. After the signing of the informed consent, they are consulted face to face. Their clinical data are included in a real time database of 106 variables in a specialized free software for electronic case report form (OpenClinica ® LLC Enterprises Services Group, USA) [19], as described in the results section. 2.2. Inclusion and Exclusion Criteria We included patients of ≥ 50 years old, cared for in the VMUH-FLS for an FF occurring in the previous 24 months. They agreed to participate in the study and gave their informed consent. FF was defined as a confirmed X-ray bone fracture, which derives from trauma that under normal conditions does not cause a fracture, after a fall from the patient’s height and without acceleration mechanism. In the case of having two or more FFs, the index was coded with the greatest impact on physical function, quality of life, and mortality (hip, vertebra, humerus, distal end of radius (DER), and any others in the same order). Exclusion criteria: (i) Patients of under 50 years of age, (ii) Patients who did not agree to participate, (iii) Patients with a noticeably short life expectancy (defined by a Paliar Index ≥ 10 points with a mortality risk at six months >61%) [ 20 ], and/or iv. Patients with trauma or pathological fractures. 2.3. Statistical Analysis In a first phase descriptive statistics were calculated with measures of central tendency and dispersion. After that, a graphic analysis was conducted, comparing the main variables by sex, age in decades, and by FF type. Finally, parametric and non-parametric tests were calculated, according to the type of variable. Both sexes were at this point compared, considering as null hypothesis of no differences between them. A two-tailed p< 0.05, with Bonferroni correction for multiple comparisons was considered significant. The statistical analysis was carried out with the STATA v 10.1 package [21]. Sample size calculations. Descriptive analysis does not require sample size calculations. All patients included in the chosen period were selected and analysed. 3. Results 3.1. VMUH-FLS Characteristics and Composition Figure 1shows both characteristics and composition. They are described below. 3.1.1. Staff and Patients The staff is composed by a secretary, two specialists in internal medicine, one rheumatologist, one case management nurse, two densitometer technicians, and three PhDs from the research group of the Andalusian Research Plan (PAIDI CTS/211). The clinical coordinator is an internist physician (FJOM), who relies on the case management nurse (MDJM). The head of the group is an internist and professor at the Faculty of Medicine (MJMG). The type of patients attended are hospitalised and outpatients. J. Clin. Med. 2021,10, 4220 4 of 17 Figure 1. Scheme of the Fracture Liaison Service. VMUH Virgen Macarena University Hospital; FLS Fracture Liaison Service; FF Fragility fractures. * Assessment by the nurse and included if Paliar index ≥10. 3.1.2. Pathways of Referral The pathways are multiple, and a direct derivation from PC and various referral services serving hospitalised and outpatients is important. In addition, index cases are identified by the reviewing of emergency lists looking for codes related to FF according to the Minimum Basic Data Set of Andalusia (CMBD) [ 22 ] and the International Statistical Classification of Diseases and Related Health Problems 10th Revision (ICD-10) [23]. Regular visits are carried out to the Plaster and Emergency Room with review of outpatient lists. Surgical demand records are searched for admitted patients. There is also direct derivation by consultation sheets of the reference units (Orthopaedic Surgery and Traumatology, Rheumatology, Internal Medicine, Rehabilitation, PC, and others such as Medical and Radiotherapy Oncology, Urology, Gynaecology, and Endocrinology). 3.1.3. Flow of Patients There is a dual flow of patients to the unit: • Two-way process: The collaboration with PC is critical and involves sending patients from PC, where they are cared for with an FF. Once evaluated in VMUH-FLS, patients are referred to PC for follow-up, with the option to be re-referred to the VMUH-FLS, if needed. From the reference units, patients with an FF are referred to the VMUH-FLS and vice versa, based on an early care agreement; • One-way process: patients with an FF are derived from referral services, served in the VMUH-FLS, and referred to PC (Figure 1). 3.1.4. Referral Protocols Previous working meetings were held with all those concerned. They agreed to centralise care in VMUH-FLS. The corresponding diagnostic and treatment protocols were J. Clin. Med. 2021,10, 4220 5 of 17 agreed, based on the SEIOMM Clinical Practice Guidelines [ 24 ] and the Spanish Society of Rheumatology (SER) [ 25 ]. Signage was placed with referral instructions in Traumatology and Orthopaedics consultations, Emergency rooms, and Plaster rooms. In these areas preprinted inter consultations and lab test sheets were provided. Well-functioning pathways were established by telephone, e-mail, WhatsApp, and Tele-consultation. The referral protocols are different depending on the type of FF and are outlined in Figure 1. • Hip fracture: The patient is admitted in the emergency room service and is transferred to the Traumatology and Orthopaedics Units. They contact the Perioperative Internal Medicine Unit that proceeds with the ortho geriatric evaluation. When discharged, the patient is referred to the FLS; • DRE fracture: Most are served in the Emergency room and move to the plaster room, where they are evaluated and derived to the FLS. Those requiring surgical treatment are captured by CMBD [22] or ICD-10 [23]; • Humerus fracture. The patient is admitted through the Emergency Room. If required, they are hospitalised in Orthopaedic Surgery and Traumatology Unit. When discharged, they are derived from consultation of trauma and from there to the FLS; • Vertebral fractures. They are captured and forwarded from all reference units and from PC. 3.1.5. FLS Care It is carried out on a one-time visit that lasts approximately 3.5 h. In a day of consultation, a physician attends to 12 first visits and four reviews. There are two consultations on Tuesdays and two on Fridays. The rest is by telemedicine. Once a possible case has been identified, the nurse checks the medical history to verify that the patient meets the inclusion criteria. In this case, she contacts the patient by phone and fixes an appointment, during which, and after explaining the project and signing the consent, a physician and nurse carry out the comprehensive evaluation. The evaluation includes (i) Anamnesis, (ii) Physical examination with anthropometric measurements (weight, height, and body mass index (BMI)), (iii) Collecting sociodemographic variables, iv. Identifying the mechanism that caused the fracture, smoking, alcoholism, and personal history of fractures and history of falls and treatments, v. Estimating the risk of fracture according to the instrument Fracture Risk Assessment Tool (FRAX®) [26]. In addition, some validated Spanish versions of the following specific tests have been used: 1. Barthel scale [27]; 2. Hand grip strength by dynamometry [28]; 3. Fall risk estimation with J D Dowton Index [29]; 4. Functional performance with the Short Physical Performance Battery Scale (SPPB) [ 30 ]; 5. Screening of the nutritional status with the Mini Nutritional Assessment instrument (MNA instrument ®) [31]; 6. Generic quality of life measurement (EuroQol5D) [32]. Physicians review the results of a specific analysis: full blood count, Erythrosedimentation rate (ESR), serum levels of calcium, phosphorus, alkaline phosphatase, parathormone, 25(OH) vitamin D, total proteins, albumin, creatinine, glomerular filtration rate, thyrotropin, and tyrosine, basic urine analysis, and calcium/creatinine ratio in urine. Other tests are added according to clinical guidance (antibodies to transglutaminase and gliadin, protein electrophoresis, testosterone levels, and 24-h urine analysis or autoantibody tests). The search for morphometric vertebral FF is performed by reviewing lateral X-rays of the dorsal and lumbar spine, with a specific protocol agreed with the Radiology department. The femur neck and lumbar BDM with a dual energy X-Ray absorptiometry (Dexa Hologic Discovery densitometer®) is performed and assessed. J. Clin. Med. 2021,10, 4220 6 of 17 Comorbidity and the type and number of drugs at the time of FF are evaluated. Looking for drugs (glucocorticoids, aromatase inhibitors, therapy of prostate cancer, psychotropics, etc) related to OP and falls is important. Clinical evaluation is recorded in a real time database (OpenClinica ® ) containing 106 variables [ 20 ]. A report is obtained from the database and is computerised in the Andalusian Health Service (Diraya) [ 33 ] . With all the information the patient is re-evaluated in a single act, during which on suspicion of sarcopenia, femoral rectum muscle ultrasound is performed (ultrasound General Electric Logiq v2®). Finally, a diagnosis is made regarding OP, risk of falls, FF and a comprehensive targeted treatment plan is done for each patient. The plan includes: 1. Verbal and written explanation of OP; 2. Measures of primary prevention of falls and OP; 3. Nutrition indications; 4. Exercise plan to improve physical function; 5. A plan to reduce the risk of falls. A written report is issued, including a table of exercises aimed at improving muscle balance and function, and a specific drug treatment for OP is instructed. A copy of the report is forwarded to the PC physician. Follow-up. It is done based on risk. Patients at low and medium risk of FF and falls are referred to PC and monitoring is conducted by phone in the following 6, 12, and 24 months. Patients at high risk of FF and falls, and those with suspected poor adherence to treatment are followed in FLS with personal appointments every 3, 6, 12, and 24 months, depending on the judgment of the physician. Adherence is measured by phone or face-to-face interview; and confirmed by reviewing the dispensing of the drug through electronic prescription of the Andalusian System of Health [34]. 3.1.6. Patient Recruitment A total of 450 patients were included in an 18-month study. Of which 351 (78%) were attended to in single-act consultation. The patient flowchart is shown in Figure 2. Figure 2. Flow diagram of the 450 patients attended in the Fracture Liaison Service. J. Clin. Med. 2021,10, 4220 7 of 17 Forty patients (9%) were excluded. The causes of exclusion were a noticeably short life expectancy (Paliar index ≥ 10) in 12 (3%) patients, six patients (1%) with age <50 years, three patients (0.6%) with high-impact fractures, four patients (0.9%) with refusal to participate. In total, 15 duplicated records were removed after a database clean-up. 3.2. Clinical Characteristics and Treatment of the Patients Data from 410 patients were analysed and are shown in Table 1, aged 73.5 ( ± 10.2) with a lower limit of 51 and upper limit of 94 years. Most were women (n= 328, 80%). Table 1. Characteristics of patients. Variable Women Men Total p* n= 328 (80%) n= 82 (20%) n= 410 (100%) Mean ±SD Mean ±SD Mean ±SD Age, years 73.5 ±10.3 73.4 ±10.2 73.5 ±10.2 0.9 Age of menopause 48.9 ±5.1 Months since FF and FLS assessment 5.9 ±4.7 5.4 ±4.4 5.8 ±4.6 0.4 Weight (kg) 67.0 ±13.7 75.2 ±14.7 68.6 ±14.3 0.00001 Height (m) 1.52 ±0.06 1.64 ±0.06 1.54 ±0.08 0.00001 BMI 28.7 ±5.5 27.8 ±4.8 28.6 ±5.4 0.1 T-Score of femoral neck −2.32 ±1.11 −2.36 ±0.82 −2.33 ±1.06 0.7 T-Score of total lumbar spine −1.99 ±1.39 −1.66 ±1.60 −1.92 ±1.93 0.1 n(%) n(%) n(%) Type of fracture 0.0001 Hip 132 (40) 53 (66) 185 (45) Vertebra 81 (25) 20 (24) 101 (25) DRE 64 (20) 1 (1) 65 (16) Humerus 31 (9) 1 (1) 32 (8) Other 20 (6) 7 (8) 25 (6) Total 328 (80) 82 (20) 410 (100) Time between FF and FLS visit (months) 0–3 82 (27) 22 (29) 104 (27) 3–6 130 (43) 37 (48) 167 (44) 6–12 57 (19) 8, (10) 65 (17) 0.3 ≥12 36 (12) 10 (13) 40 (12) Total 305 (80) 77 (20) 376 (100) Age group (years) 50–59 47 (15) 12 (15) 59 (15) 0.9 60–69 71 (22) 20 (25) 91 (23) 70–79 110 (34) 25 (31) 135 (34) 80–89 85 (27) 22 (27) 107 (27) ≥90 8 (2) 1 (1) 9 (2) Total 321 (80) 80 (20) 401 (100) Current smoking 37 (12) 27 (34) 64 (16) 0.0001 Alcoholism >3 units/day 16 (5) 19 (24) 35 (9) 0.0001 Secondary OP 41 (15) 17 (27) 58 (17) 0.02 BMD femoral neck Osteoporosis 138 (47) 28 (14) 160 (46) 0.3 Osteopenia 97 (33) 32 (46) 129 (35) 0.03 Normal 60 (20) 9 (13) 69 (19) 0.1 BMD total lumbar spine Osteoporosis 120 (40) 24 (35) 144 (39) 0.4 Osteopenia 78 (26) 14 (21) 92 (25) 0.3 Normal 100 (34) 30 (44) 130 (36) 0.1 BMI ≤19 9 (3) 0 (0) 9 (2) 0.1 BMI ≥30 125 (38) 32 (40) 157 (38) 0.7 Calcium intake in diet ≤1000 mg/day 142 (44) 30 (38) 172 (43) 0.3 >1000 mg/day 180 (56) 44 (62) 229 (57) Regular exercise J. Clin. Med. 2021,10, 4220 8 of 17 Table 1. Cont. Variable Women Men Total p* n= 328 (80%) n= 82 (20%) n= 410 (100%) Daily exercise 44 (15) 5 (7) 49 (13) 0.0001 Stroll on the street 141 (47) 36 (48) 177 (47) Wander at home 87 (29) 15 (15) 102 (27) Bed-armchair 29 (10) 19 (25) 48 (13) Total 301 (80) 75 (20) 376 (100) FLS referral unit Orthopaedic surgery and traumatology 134 (41) 27 (34) 161 (40) Perioperative internal medicine 101 (31) 39 (49) 139 (34) Rheumatology 39 (12) 7 (9) 46 (11) 0.004 Others 38 (12) 7 (9) 45 (11) Emergency room and plaster room 5 (3) 0 (0) 5 (3) Total 320 (100) 80 (100) 410 (100) Pre-FF OP treatment None 262 (49) 69 (93) 331 (86) Specific treatment 49 (16) 5 (7) 54 (16) 0.02 Total 311 (81) 74 (19) 385 (100) Treatment for OP after FF None 146 (47) 27 (36) 173 (50) Specific treatment 165 (53) 47 (63) 212 (55) 0.1 Total 311 (80) 74 (20) 385 (100) Treatment for OP after FLS None 0 (0) 0 (0) 0 (0) Specific treatment 310 (100) 73 (100) 383 (100) OP Osteoporosis, SD Standard deviation, FF Fragility Fracture, FLS Fracture Liaison Service, BMI Body mass index. DRE Distal radius end. BMI Bone mineral densitometry. * Comparison between women and men. There were no differences between women and men in terms of age, referral time, or BMI, but in weight and height. Men were taller and heavier, as expected. There were clinical and statistical differences in the type of FF (Table 1and Figure 3). Figure 3. Type of bone fragility fractures in all patients and by sex. No hip-No vertebral fragility fractures include distal radius end n= 65 (16%), humerus n= 32 (8%), tibia n= 5 (1%), fibula n= 4 (0.9%) , tibia and fibula n= 4 (0.9%), ribs n= 4 (0.9%), pelvic fracture n= 4 (0.9%), elbow n= 2 (0.4%), patella n= 2 (0.4%) and one distal femur. J. Clin. Med. 2021,10, 4220 9 of 17 Hip FF was more common in men, whereas DRE and humerus was more common in women. Vertebral FF and the Other FF group had equal gender distribution. In 11% of cases two or more FF were found. This percentage ranged from 5% to 12% in patients with first hip, vertebral, and DRE FF and rose to 67% in the group with other FFs. The anatomic sites of the second FF were vertebral n= 9 (21%), DRE n= 6 (14%), tibia n= 6 (14%) , and+ fibula n= 4 (9%). Two-thirds of patients were evaluated in the FLS within 6 months after the index FF. Most of the FF occurred in patients between 70 to 79 years of age, followed by patients of age between 80 to 89 years, with no gender differences. The prevalence of smoking was three times higher in men. The prevalence of alcoholism was five times higher. Additionally, secondary causes of OP were commonly found in men. In addition, they had lower physical activity. There were differences in the referral units to FLS, related to type of FF. Sex Differences The most important gender difference was the low percentage of patients receiving OP specific treatment prior to FF; 49 (16%) women versus 9 (7%) men had been treated at some point in their life before the FF, p= 0.04. After the FF, specific treatment for OP was started in the reference unit in 271 (86%) women versus 48 (63%) men (Table 1and Figure 4). Figure 4. Specific treatment for osteoporosis previous and after the Fracture Liaison Service in all patients and by sex. FF Fragility fracture FLS Fracture Liaison Service. All patients, both women and men were treated after the VMUH-FLS intervention. The probability for a man not to receive treatment at some point prior to FF was 2.5 (CI95% J. Clin. Med. 2021,10, 4220 16 of 17 18. Hospital Universitario Virgen Macarena. Nuestro Hospital. Memoria. 2014. Available online: https://www.hospitalmacarena.es/ memoria/ (accessed on 28 February 2021). 19. Clinical Data Management. 2010. 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