Active identification of vertebral fracture in the FLS model of care.

The identification of vertebral fracture is a key point in an FLS. We have analyzed the characteristics of 570 patients according to the route of identification (referral by other doctors, emergency registry or through VFA), concluding that promoting referral by other doctors with a training campaign is effective. PURPOSE: Vertebral fractures (VF) are associated with increased risk of further VFs. Our objective was to analyze the characteristics of patients with VF seen in a Fracture Liaison Service (FLS). METHODS: An observational study was carried out on patients with VF referred to the outpatient metabolic clinic (OMC) after a training campaign, identified in the emergency registry, and captured by VF assessment with bone densitometry (DXA-VFA) in patients with non-VFs. Patients with traumatic VF or VF > 1 year, infiltrative or neoplastic disease were excluded. The number and severity of VFs (Genant) were analyzed. Treatment initiation in the first 6 months after baseline visit was reviewed. RESULTS: Overall, 570 patients were included, mean age 73. The most common route for identifying VF was through referral to OMC (303 cases), followed by the emergency registry (198) and DXA-VFA (69). Osteoporosis by DXA was found in 312 (58%) patients and 259 (45%) had ≥ 2 VFs. The rate of grade 3 VFs was highest among patients on the emergency registry. Those identified through OMC had a higher number of VFs, a higher rate of osteoporosis, more risk factors and greater treatment initiation. Patients with VFs detected by DXA-VFA were mostly women with a single VF and had a lower rate of osteoporosis by DXA. CONCLUSIONS: We present the distribution of VFs by the route of identification in an FLS. Promoting referral by other doctors with a training campaign may help in the quality improvement of the FLS-based model of care.

Implications of FRAX® adjusted for recent fracture on the indication of treatment in an FLS.

We analyzed the practical consequences of applying an adjusted FRAX® for recent fractures in a FLS. After analyzing 2777 patients, we concluded that the adjusted FRAX® is irrelevant when calculating FRAX® with DXA and is only useful for fractures of the humerus when DXA is not available. PURPOSE: A FRAX® adjusted to fractures less than 2 years old has been proposed. The objective of this work was to analyze the clinical implications of applying the adjusted FRAX® instead of the classic FRAX® in a fracture liaison service (FLS) unit. METHODS: Adults aged 50 years or older with fragility fractures (hip, spine, humerus, and forearm) that occurred in the 12 months prior to the baseline visit were included. We recorded demographic data, type of fracture, DXA, classic FRAX®, and FRAX® adjusted for recent fractures and indications for anti-osteoporotic medication (AOM) following the guidelines of the Spanish Society of Rheumatology. RESULTS: A total of 2777 patients were included, mean age 73 years, 84% women. The type of fracture was as follows: forearm (n = 958; 34.5%), hip (n = 781; 28.1%), humerus (n = 642; 23.1%), and spine (n = 397, 14.3%). DXA was performed in 2134 cases (76.8%). A total of 2522 patients (90.8%) were candidates for AOM (100% involving the hip and spine, 83% forearm, and 85% humerus). FRAX®-hip ≥ 3% increased from 1601 to 1775 cases (57.6 to 64%). The average FRAX®-hip (SD) increased from 5.7 (6) to 7.5 (9) (4.6 to 8.8 in males and 5.9 to 7.3 in females). The percentage of forearm fracture candidates for AOM, with or without DXA, did not change after FRAX®-hip adjustment, while the number of patients with humerus fractures increased from 59 to 80% in those who did not have DXA. In the entire sample, FRAX®-adjusted led to an indication of AOM for 15 additional patients (0.5% of major fractures): 14 with a humerus fracture and 1 with a forearm fracture. CONCLUSIONS: The adjusted FRAX® for recent fractures in an FLS unit in an adjusted FRAX® is irrelevant when calculating FRAX® with DXA; in fact, it is only useful for fractures of the humerus when DXA is not available.

Long-term persistence of treatment after hip fracture in a fracture liaison service.

Long-term adherence to antiosteoporosis medication (AOM) in the setting of a fracture liaison service (FLS) are not well known. Patients ≥ 50 with hip fracture seen in an FLS and recommended for treatment to prevent new fractures were analyzed. Baseline data included demographics, identification mode, previous treatment and FRAX items. Patient records were reviewed 3-8 years later, and these data were collected: (1) survival; (2) major refracture; (3) initiation of treatment, proportion of days covered (PDC) and persistence with AOM. 372 patients (mean age, 79 years; 76% women) were included. Mean follow-up was 47 months, 52 patients (14%) had a refracture (22 hip) and 129 (34.5%) died. AOM was started in 283 patients (76.0%). Factors associated with initiation of AOM were previous use of bisphosphonate (OR 9.94; 95% CI 1.29-76.32) and a lower T-score lumbar (OR 0.80; 95% CI 0.65-0.99). Persistence decreased to 72.6%, 60% and 47% at 12, 36 and 60 months. A PDC > 80% was confirmed in 208 patients (55.7%) and associated with previous use of bisphosphonate (OR 3.38; 95% CI 1.34-8.53), treatment with denosumab (OR 2.69; 95% CI:1.37-5.27), and inpatient identification (OR 2.26; 95% CI 1.18-4.34). Long-term persistence with AOM was optimal in patients with hip fracture seen at an FLS. A PDC > 80% was associated with inpatient identification and prescription of denosumab.

Fracture liaison service model: treatment persistence 5 years later.

We analyzed the long-term persistence of treatment in a FLS. During follow-up, 15.2% of patients had a refracture and 23.8% died. At the 5-year checkup, 74% had started treatment (associated with female sex, previous use of bisphosphonate, and referral to an osteoporosis clinic). Persistence at 1 and 5 years was 70.6% and 46.5%, respectively. INTRODUCTION: To analyze the long-term persistence of treatment in a fracture liaison service (FLS). METHODS: Patients ≥ 50 years with a fragility fracture attended between 2012 and 2016 who were recommended for treatment to prevent new fractures were included. Baseline data included demographics, type of fracture, previous treatment, and FRAX® items. Five years later, patient records were reviewed and the following data were collected: [1] survival; [2] refracture; [3] initiation of treatment, persistence, and medication possession ratio (MPR) > 80%. RESULTS: We included 888 patients, mean age 75 years, 83% women, and mean follow-up 56 months. During follow-up, 135 patients (15.2%) had a refracture (109 major fractures, 50 hip refractures) and 212 patients died (23.8%); at the 5-year checkup, 657 patients (74%) had started some type of treatment. Factors associated with the start of treatment were female sex (OR 2.10; 95% CI: 1.42-3.11), previous use of bisphosphonate (OR 3.91; 95% CI: 2.23-6.86), and referral to an osteoporosis clinic (OR 1.46; 95% CI: 1.02-2.07). Persistence decreased from 70.6% at 12 months to 46.5% at 60 months. An MPR > 80% was confirmed in 449 patients, 68.3% of whom were under treatment. A total of 521 and 447 patients received treatment for at least 24 and 36 months, respectively (79.3% and 68.0% of those who started treatment). CONCLUSIONS: Patients with fragility fractures attended at an FLS showed optimal long-term persistence of treatment. These data can help healthcare managers better calculate the cost-effectiveness of implementing the FLS model.

The evolution of an FLS in search of excellence: the experience of Gran Canaria.

We present the achievements and difficulties of our pioneering FLS within the Spanish public health system over an 8-year period. Despite implementing consolidating measures at the unit, the addition of a support nurse, the establishment of a solid alliance with primary care, the involvement of primary care nurses, and starting initial prescriptions at the hospital are pending. PURPOSE: To assess the consolidation of an FLS after its implementation as well as the problems that have arisen over time. METHODS: The program for secondary fracture prevention was implemented in 2012. Initially manned by the same staff assigned to the rheumatology department, a part-time support nurse was added in 2016. Patients were identified from the emergency registry and, more recently, from among those admitted for hip fracture and treated in a monographic osteoporosis clinic. The baseline visit consisted of a consultation with the nurse, as well as DXA and bone metabolism analytics. Patients were referred to their primary care physician to start treatment. RESULTS: Of the 2416 attended patients, 30% presented forearm fractures, 27% hip, 20% humerus, 10% spine, and 11% other fractures. In comparison with 2012, in 2019, the monthly average of patients had doubled, with an increased in the number of hip and spine fractures and an increase in the percentage of captured patients. The performance of DXA fell from 100 to 52%, and fewer patients were referred to the osteoporosis clinic. One in four patients was referred to a fall prevention school. Despite implementing consolidating measures at the unit (the addition of a support nurse and the establishment of a solid alliance with primary care), the involvement of primary care nurses and starting initial prescriptions at the hospital are pending. CONCLUSIONS: We present herein the achievements made by our FLS and the difficulties within the Spanish public health system over an 8-year period.

Impact of the implementation of a Fracture Liaison Service on pharmaceutical expenses for osteoporosis compared to an area without an FLS.

INTRODUCTION: Fracture Liaison Service (FLS) model for secondary prevention of fractures has demonstrated its cost-effectiveness using decision models. We analyze the impact of a FLS on pharmaceutical expenditures for osteoporosis (OP) in real-world circumstances. METHODS: Expenditures on OP medications from January 2011 to January 2017 were compiled. Pharmaceutical expenditures in the southern area of Gran Canaria were used as a control group to measure the impact of implementing an FLS in the northern area. We estimated generalized least squares regressions with interrupted time-series analysis where two interventions were considered: March 2012 (implementation of the FLS) and March 2016 (incorporation of nursing staff for inpatients with hip fracture). RESULTS: The northern area incurred greater expenditures for group I and II drugs. The difference in bisphosphonates expenditures between areas varied from 10.5% higher in the northern area pre-FLS to 11.2% post-FLS and 18.3% since March 2016. However, interrupted time series models do not find a significant impact of implementation of FLS on the pharmaceutical expenditures for either drug group. CONCLUSION: The implantation of an FLS did not lead to an increase in pharmaceutical expenditures for OP over the 5-year period compared to the standard care provided for secondary fracture preventions.

Local unfolding is required for the site-specific protein modification by transglutaminase.

The transglutaminase (TGase) from Streptomyces mobaraensis catalyzes transamidation reactions in a protein substrate leading to the modification of the side chains of Gln and Lys residues according to the A-CONH(2) + H(2)N-B → A-CONH-B + NH(3) reaction, where both A and B can be a protein or a ligand. A noteworthy property of TGase is its susbstrate specificity, so that often only a few specific Gln or Lys residues can be modified in a globular protein. The molecular features of a globular protein dictating the site-specific reactions mediated by TGase are yet poorly understood. Here, we have analyzed the reactivity toward TGase of apomyoglobin (apoMb), α-lactalbumin (α-LA), and fragment 205-316 of thermolysin. These proteins are models of protein structure and folding that have been studied previously using the limited proteolysis technique to unravel regions of local unfolding in their amino acid sequences. The three proteins were modified by TGase at the level of Gln or Lys residues with dansylcadaverine or carbobenzoxy-l-glutaminylglycine, respectively. Despite these model proteins containing several Gln and Lys residues, the sites of TGase derivatization occur over restricted chain regions of the protein substrates. In particular, the TGase-mediated modifications occur in the "helix F" region in apoMb, in the ß-domain in apo-α-LA in its molten globule state, and in the N-terminal region in fragment 205-316 of thermolysin. Interestingly, the sites of limited proteolysis are located in the same chain regions of these proteins, thus providing a clear-cut demonstration that chain flexibility or local unfolding overwhelmingly dictates the site-specific modification by both TGase and a protease.