Association between High Levels of Parathyroid Hormone and Frailty: The Nepean Osteoporosis and Frailty (NOF) Study.

BACKGROUND: Frailty is associated with poor outcomes hence identification of risks factors is pivotal. Since the independent role of parathyroid hormone (PTH) in frailty remains unexplored, we aimed to determine this in a population of older individuals with a history of falling. DESIGN: Cross-sectional study. SETTING: Falls and Fracture Clinic, Nepean Hospital (Penrith, Australia). PARTICIPANTS: 692 subjects (mean age=79, 65% women) assessed between 2009-2015. MEASUREMENTS: Assessment included clinical examination, mood, nutrition, grip strength, gait velocity, bone densitometry and posturography. Chemistry included serum PTH, calcium, vitamin D (25(OH)D3), creatinine and albumin. Normocalcemic subjects were divided into 4 groups: (1) Normal: 25(OH)D3 >50nmol/L and PTH between 1.6-6.8pmol/L; (2) PTH responsive: low 25(OH)D3 (<50nmol/L) and high PTH (>6.8pmol/L); (3) PTH unresponsive: low 25(OH)D3 and normal PTH; (4) Hyper PTH (>6.8pmol/L) with normal 25(OH)D3. Frailty was defined using Fried's criteria. Difference between the groups was assessed using one-way ANOVA and X2 analysis. Multinomial logistic regression evaluated the association between the groups and the number of Fried's criteria adjusted for age, BMI, renal function, 25(OH)D3 levels, and albumin. RESULTS: 22.6% subjects had high PTH levels (>6.8pmol/L). All subjects in the high PTH groups had significantly lower grip strength, gait velocity, limits of stability, and higher BMI. The PTH responsive group had a higher risk of pre-frailty (ß=3.8, 95% CI = 3.42 - 5.22, p≷ 0.01) and frailty (ß=8.26, 95% CI = 2.8-16.1, p<0.01). The risk of frailty was also higher in the Hyper PTH group (ß=2.3, 95% CI = 1.74-4.32, p<0.01). CONCLUSION: We have reported an independent association of high PTH levels with high number of falls and with the clinical components of physical frailty in community dwelling older persons. Our results suggest a possible role of PTH in frailty that deserves further exploration.

Comprehensive nutritional status in sarco-osteoporotic older fallers.

OBJECTIVES: In older persons, the combination of osteoporosis and sarcopenia has been proposed as a subset of frailer individuals at higher risk of falls and fractures. However, the particular nutritional status of the sarco-osteoporotic (SOP) patients remains unknown. The goal of this study was to obtain a comprehensive picture of nutritional status in SOP patients. DESIGN: Cross-sectional study. SETTING: Falls and Fractures Clinic, Nepean Hospital (Penrith, Australia). PARTICIPANTS: 680 subjects (mean age=79, 65% female) assessed between 2008-2013. MEASUREMENTS: Assessment included medical history, mini-nutritional assessment, physical examination, bone densitometry and body composition by DXA, and blood tests for nutritional status (albumin, creatinine, hemoglobin, vitamin D, vitamin B-12, calcium, phosphate and folate). Patients were divided in 4 groups: 1) osteopenia/osteoporosis (BMD<-1.0 SD); 2) sarcopenia; 3) SOP; and 4) normal (no sarcopenia/no osteoporosis). Difference between groups was assessed with one-way ANOVA and chi square analysis. Multivariable linear regression evaluated the association between the groups and measures of nutritional parameters. RESULTS: Sarcopenia was present in 47.4% of those with osteopenia (167/352) and 62.7% in those with osteoporosis (91/145). Mean age of the SOP was 80.4±7 years. SOP patients showed significantly higher prevalence of falls and fractures. Univariate analyses showed that SOP were more likely than normal to have a BMI< 25 (OR 2.42 95%CI 1.45-4.041, p<0.001), a MNA score <12 (OR 2.0, 95%CI 1.15-3.49, p<0.05), serum folate <20 nmol/L (OR 4.0 95%CI 1.35-11.87, p<0.01) and hemoglobin <120g/L (OR 2.0 95%CI 1.28-3.30, p<0.01). Multivariate analysis showed that a MNA score <12 was independently associated with SOP compared to normal when adjusted for age and gender. Hemoglobin <120g/L, BMI <25, and GDS >6 remained independently associated with SOP after adjustment for all variables including inflammatory conditions. Hypoalbuminemia (<35 g/L) was associated with just osteopenia/osteoporosis (OR: 2.03, 95%CI 1.08-3.81, p<0.01) and just sarcopenia (OR: 1.77, 95%CI 1.0-3.0, p<0.01) compared to normal. No differences in vitamin D, glomerular filtration rate, albumin, corrected calcium, phosphate, red blood cells folate or vitamin B12 levels were found between the subgroups. CONCLUSIONS: In approaching SOP patients, early prevention protocols directed to optimize their nutritional status would be a key strategy to prevent poor outcomes such as falls and fractures in this high risk population. Therefore, nutritional assessment and early nutritional supplementation should be essential domains in this strategy.

Vitamin D status in relation to postural stability in the elderly.

OBJECTIVES: Postural instability (PI) is an important risk factor for falls, especially in the frail older population. In this study, we investigated the impact of vitamin D deficiency on PI in a sample of community dwelling older subjects. Our objective was to determine the potential association between vitamin D deficiency and PI in older fallers. DESIGN: Cross-sectional study. SETTING: Falls and Fractures Clinic, Department of Geriatric Medicine, Nepean Hospital, Penrith, Australia. PARTICIPANTS: One hundred and forty-five adults aged 65 years and older who have had at least one episode of a fall within the six months prior to assessment at the Falls and Fractures Clinic. MEASUREMENTS: Serum 25(OH) vitamin D3 [25(OH)D3] and parathyroid hormone concentrations were determined at baseline. Subjects were separated into 3 groups based on serum 25(OH)D3 levels with the following cut-off values: < 30 nmol/L (deficient), 30-50 nmol/L (insufficient) and > 50 nmol/L (normal). Other baseline measurements included body mass index, mini-nutritional assessment, grip strength, serum calcium concentration and creatinine clearance, which were used as covariables. PI was assessed using a computerized virtual reality system (Medicaa, Uruguay). Measured parameters included limits of stability (LOS) and centre of pressure (COP) under eyes closed on foam (ECF) and visio-vestibular stimulation. The estimated swaying area, computed from the ellipse of confidence under eyes closed standing on foam (ECF), was also used as a PI parameter. Gait velocity (GV) was measured using a GaitRITE walkway system. RESULTS: Posture was impaired in vitamin D deficiency (<30 nmol/L) as indicated by lower LOS (90 +/- 18), higher ECF (25 +/- 10) and slower GV (55 +/- 7) as compared with the insufficient and normal groups. After adjustment for demographic, biochemical and anthropometric variables, vitamin D deficiency significantly correlated with low LOS and high COP under ECF. CONCLUSION: Low levels of vitamin D were associated with PI. This association could also have an effect on slow GV and increased risk of falls. In conclusion, using an objective method to measure balance in older fallers we have identified a novel role of vitamin D in balance control. Prospective studies are required to confirm the effect of vitamin D on PI and elucidate the mechanisms of this association.