Vitamin D replenishment and vitamin D status in functional outcomes following hip fracture surgery

Abstract

Background: Older people presenting with hip fractures requiring surgery have a high prevalence of hypovitaminosis D, which is an important modifiable risk factor for falls and fractures. Inadequate sun exposure is the main reason for vitamin D deficiency in older people. Vitamin D supplements, with or without calcium have been shown to reduce falls and fracture risk in this population. Undertreated pain is a risk factor for delirium and a barrier to rehabilitation interventions following a hip fracture. A small number of randomised controlled trials (RCTs) have shown increased 25-OHD levels with a loading dose of vitamin D may improve falls and fractures. Low vitamin D levels have also been implicated in pain generally, as well as static and dynamic pain responses to mobility. It is not known whether oral vitamin D replenishment using a loading dose is effective, and if it is, what is the interplay this is with patient characteristics, in particular self-reported pain rating levels, lower limb mobility and 25-OHD levels. Aims: The aims of this research were (1) to characterise the predictive factors of 25-OHD levels; (2) to characterise the predictive factors of self-reported pain after hip fracture; (3) to determine the benefit of early loading-dose oral vitamin D replenishment and determine the 25-OHD response; (4) to evaluate safety profile of an initial high-dose (250,000IU) vitamin D followed by daily maintenance for 6 months; (5) to monitor its effects on functional mobility, falls, fractures, grip strength, health related quality of life and mortality. Methods: Participants of the REVITAHIP RCT cohort (mean age of 220 participants was 83.9 (SD 7.2) years and 77.1% were women): Active (111) and Placebo (107) participants were randomised to loading dose (250000IU vitamin D3) vs placebo followed by 6 months maintenance oral therapy (vitamin D3/calcium: 800IU/600mg) daily. Primary outcome measures are 2.4m gait-velocity, with secondary outcome measures of falls, fractures (Week-4), 25-OHD levels, quality-of-life measure (EQ-5D), mortality at weeks-2, 4 and 26 with additional measures of pain (via the numerical rating scale [NRS]) were correlated with patient characteristics in this cohort. Results: Hypovitaminosis D (25-OHD <50nmol/L) was present in 46.8% of participants and 15.4% had 25-OHD levels lower than 30nmol/L. Multivariate regression models demonstrated higher baseline vitamin D levels were significantly associated with higher premorbid Barthel Index scores and lower post-operative NRS pain levels. Further, the mean (SD) NRS pain score was 3.5 (2.3). More than half (61.9%, n=113) had NRS>3 and 18.1% (n=52) had NRS>5. Using the EQ-5D pain sub-score, 78.1% had moderate pain or discomfort and 7.9% had extreme pain or discomfort. Using a multivariate regression model, postoperative NRS was significantly higher in persons with a higher comorbidity count, those previously living independently alone, and surgical fixation with hemiarthroplasty. After loading dosing administration, 25-OHD levels were significantly higher for the Active group when compared to the Placebo group at 2 weeks (73 vs 66 nmol/L; p=.019) and at 4 weeks (83 vs 75nmol/L; p=.030). At week 4, the Active group had a significantly lower percentage of people with suboptimal 25-OHD levels (3.2% vs 15.4%, p=.019). At week 4, participants in the Active group had a gait velocity over 2.4m of 0.42m/s compared with 0.39m/s in the placebo group (p=.490). To week 4, seven (6.3%) participants in the Active group reported 1 or more falls compared to twenty-three (21.1%) in the Placebo group (χ2 = 4.327; p=.024) but there were no differences in fractures (2.7% vs 2.8%, p=.964) or grip strength. The number of deaths was non-significantly lower in the Active group compared with the Placebo group at 4 weeks (1 vs 3, p = .295). There was a trend for Active participants to have a higher total EQ-5D scores at Week 26 (88.1+/-13.2 vs 84.3+/-15.8, F=2.87, p=.092). Active participants were significantly more likely to present with ‘no pain or discomfort’ at Week 26 (96.4% vs 88.8%, p=.037). One case of hypercalcemia at 2 weeks was noted in the Active group which normalised after 4 and 26 weeks. Discussion and Conclusions: This study cohort shared similar demographic characteristics and comorbidities with other cohorts of people with hip fracture. Hypovitaminosis D was not as prevalent as previously documented. Patients taking vitamin D supplements and with higher premorbid Barthel Index, reflecting greater independence and activity, tended to have higher 25-OHD levels at baseline. Further, lower NRS pain ratings following surgery were associated with higher vitamin D levels. Overall, the levels of pain reported by this cohort are acceptable although approximately 10% to 15% had higher than reasonable levels of pain. Despite a higher than expected baseline 25-OHD level and moderate increases in 25-OHD levels, participants in the Active REVITAHIP group resulted in a greater percentage with target 25-OHD levels (>50nmol/L) compared with the placebo group with no significant differences in gait velocity at 4 weeks. Lower numbers of falls and improved pain control were noted in the Active group over the study period. In this cohort, there was a higher than expected baseline 25OH level which could have underestimated the effect of the intervention in a group with lower baseline 25-OHD levels.