HIP FRACTURES IN OLDER ADULTS AND TREATMENT WITH INTRAVENOUS ZOLEDRONIC ACID

Abstract

Introduction: Osteoporotic hip fractures are common in older adults and are responsible for significant morbidity and mortality. Structured geriatric care for older adults with hip fracture is known to improve outcomes. A large body of evidence also exists for treatment of osteoporosis with intravenous zoledronic acid (IVZA), but there is limited evidence of its efficacy and safety when given soon after fracture. Aims: I aimed to test the hypothesis that the successful administration of an integrated care pathway for older adults with hip fracture results in positive outcomes with regard to inpatient complications and morbidity and mortality at one year. I also aimed to test the hypothesis that IVZA for osteoporosis is tolerable, safe and efficacious when given to patients during their inpatient admission following hip fracture. I further aimed to test the hypothesis that IVZA, when administered early post fracture, results in a significant improvement in bone mineral density and suppression of biochemical markers of bone turnover. Lastly, by means of comparison, I examined differences between the characteristics of my study participants, and those of a similar community dwelling cohort who had previous history of hip fracture. Methods: The primary study population comprised patients admitted to St James s Hospital Dublin with acute hip fracture in 2015-2016. The secondary population were community-dwelling older Irish adults with a history of hip fracture, who were already recruited in the Trinity, University of Ulster, Department of Agriculture (TUDA) study. Acute hip fracture participants received IVZA, calcium and vitamin D supplements and blood tests and bone mineral density assessment using Dual Energy X-ray Absorptiometry (DXA were done at baseline and 1-year). I also collected information on participant demographics and medical history, inpatient complications and mortality over one year. Biophysical measures including hand grip strength were assessed. Results: 165 participants were enrolled into the Acute Hip Fracture cohort (66.6% female; mean age 78.4±10.9). There was a high prevalence of frailty (median Clinical Frailty Score (CFS) 5) comorbidities (median Charlson Comorbidity Index (CCI) 5). 97% of fractures occurred due to a fall, though only 6.1% reported syncope; 46.1% had a fall in the year prior. There was a low prevalence of a prior diagnosis of osteoporosis (12.1%) and an even lower proportion were on osteoporosis therapy prior to admission (9.7%). Only 26.7% had replete 25 hydroxyvitamin D (25(OH)D levels (>=50 nmol/l) and only 7.9% were taking a vitamin D supplement. The most significant post-fracture complications were delirium (33%), constipation (43%) and lower respiratory tract infections (23%). Delirium was correlated with higher ASA grade (p=0.023), CFS (p=0.003) and constipation (p<0.0005), while lower respiratory tract infections were associated with dysphagia (p<0.001). 82% had surgery within 48 hours. 97.6% were admitted to an orthopaedic ward, but only 15.7% within target time of 4 hours. All participants had geriatrician and bone health reviews. Incidence of new pressure ulcers was 5.5%. Higher pre-fracture Barthel Index (BI) was associated with shorter time-to-surgery (p<0.0001); longer time-to-surgery was associated with longer length of stay (p=0.044) and delirium(p=0.012). Inpatient mortality was 3.6%; 20% 1-year mortality. CCI correlated with 6-month mortality (p=0.047). One year mortality was associated with lower pre-fracture BI (p=0.002) and higher CFS (p=0.009). There was significant reduction in mortality in participants whose care was transferred to a geriatrician during their inpatient admission (11.3% vs 24.1%, p=0.04, Fisher s exact test). Discharge to nursing home was associated with lower pre-fracture BI (p=0.025) and New Mobility Score (NMS) (p=0.018), and higher CFS (p=0.024). All participants received IZVA (5mg) infusion. 10.1% developed new flu-like symptoms, which were associated with higher pre-infusion CRP (p=0.017), post-operative blood transfusion (p=0.001). Overall, there was no significant difference between pre-and post-infusion renal function (p=0.82). However, there were two cases of acute kidney injury, which were attributable to causes other than IVZA. 17.2% had an episode of new hypocalcaemia post-infusion, which was associated with a lower baseline 25 (OH)D (p=0.001). New atrial fibrillation occurred in 4 participants and was associated with pneumonia (p=0.042). Baseline bone turnover markers (BTMs) were available in 161 participants. There was significant suppression of CTX (p<0.0001) and P1NP (p<0.001), but not osteocalcin (p=0.695) at 1-year follow-up in 81 participants where data was available. There were numerous correlates of changes in BTMs including suppression of CTX with lower baseline vitamin D (p=0.027) and higher serum calcium (p=0.011). 117 participants had an initial DXA; 66% had osteoporosis by DXA, 30% osteopaenia: 4% normal bone mineral density (BMD). BMD increased significantly at all measured sites: +6.0% at spine (p<0.0001); +5.8% at total hip (p<0.0001); and +3.0% at neck of femur (p=0.0015). BMD increase at spine (p=0.039) and total hip (p=0.041) was associated with higher baseline BMI; polypharmacy was associated with poorer gains in BMD of spine (p=0.037). Baseline 25(OH)D correlated negatively with change in BMD at total hip (p=0.002) and neck of femur (p=0.016), as did serum thyroid-stimulating hormone (TSH) (p=0.035 and p=0.009 respectively). The correlations between suppression of the various BTMs and changes in BMD of the spine, total hip and neck of femur were mixed. Six participants had a new fracture over 1-year follow-up. Conclusion: The characteristics of my cohort were similar to contemporaneous national and international groups. There was a high burden of frailty, comorbidities, undiagnosed and untreated osteoporosis and hypovitaminosis D. Orthogeriatric care was associated with fewer inpatient complications and lower 1-year mortality. Transition to geriatrician care was associated with lower mortality. Comorbidities and lower pre-fracture function were linked to poorer outcomes including longer length of stay, functional loss, discharge to nursing home and mortality. My results show IVZA is safe and well-tolerated when given early after fracture and was associated with low risk of hypocalcaemia, mainly in those with lower vitamin D. Suppression of BTMs and improvement in BMD was similar to other studies. The association between higher baseline vitamin D and poorer suppression of BTMS and lower gains in BMD could be elucidated by further research. My study demonstrates the utility of orthogeriatric care, the safety and efficacy of IVZA given early after fracture, and the impact of frailty, comorbidities and pre-fracture function on the ability to recover following hip fracture.