[Pharmacolgic osteoporosis treatment of nursing home residents]. / Medikamentöse Osteoporosetherapie bei Altersheimbewohner/-innen.

INTRODUCTION: Fragility fractures in older people are common and are often associated with nursing home admission in frail people. Only few institutionalized residents with documented osteoporosis receive pharmacologic osteoporosis treatment. Studies demonstrating the benefit of osteoporosis drug therapy in this multimorbid and vulnerable population are lacking.

Effects of vitamin D3, omega-3 s and a simple strength training exercise program on bone health: the DO-HEALTH randomized controlled trial.

INTRODUCTION: Evidence on the effects of Vitamin D, omega-3 s and exercise on aBMD in healthy older adults is limited. We examined whether vitamin D3, omega-3 s, or a simple home-based exercise program (SHEP), alone or in combination, over three years, improve lumbar spine (LS), femoral neck (FN) or total hip (TH) aBMD assessed by DXA. METHODS: aBMD was a secondary outcome in DO-HEALTH, a 3-year, multicenter, double-blind, randomized 2 × 2 × 2 factorial design trial in generally healthy older adults age ≥ 70 years. The study interventions were vitamin D3 (2000IU/d), omega-3 s (1 g/d), and SHEP (3 × 30 min/wk), applied alone or in combination in 8 treatment arms. Mixed effect models were used adjusting for age, sex, BMI, prior fall, study site and baseline level of the outcome. Main effects were assessed in the absence of an interaction between the interventions. Subgroup analyses by sex, physical activity level, dietary calcium intake, serum 25(OH)D levels, and fracture history were conducted. RESULTS: DXA scans were available for 1493 participants (mean age 75 years; 80.4% were physically active, 44% had 25(OH)D levels <20 ng/ml). At the LS and FN sites, none of the treatments showed a benefit. At the TH, vitamin D vs. no vitamin D treatment showed a significant benefit across 3 years (difference in adjusted means [AM]: 0.0035 [95% CI 0.0011, 0.0059] g/cm2). Furthermore, there was a benefit for vitamin D vs. no vitamin D treatment on LS aBMD in the male subgroup of (interaction P = 0.003; ∆AM: 0.0070 [95% CI 0.0007, 0.0132] g/cm2). CONCLUSIONS: Omega-3 and SHEP had no benefit on aBMD in healthy, active and largely vitamin D replete older adults. Our study suggests a small benefit of 2000 IU vitamin D daily on TH aBMD overall and LS aBMD among men, however, effect sizes were very modest and the clinical impact of these findings is unclear.

Vitamin D, omega-3 fatty acids (omega-3 s) and strength training are simple but promising strategies to improve bone health, however, their effect in healthy older adults over a period of three years was unclear. In this study, we examined whether daily vitamin D supplementation (2000 IU/d), daily omega-3 s supplementation (1 g/d) or a simple strength training program performed three times per week, either applied alone (e.g., only vitamin D supplements) or in combination (e.g., vitamin D and omega-3 s supplements) could improve bone density at the spine, hip or femoral neck. We included 1493 healthy older adults from Switzerland, Germany, France and Portugal who were at least 70 years of age and who had not experienced any major health events in the five years before study start. Taking omega-3 s supplements showed no benefit for bone density. Similarly, the simple strength exercise program showed no benefit. In contrast, participants receiving daily vitamin D supplements experienced a benefit at the hip. However, it should be noted that the effect across three years was very small.

Effects of testosterone and vitamin D on fall risk in pre-frail hypogonadal men: a factorial design RCT.

OBJECTIVE: To test whether transdermal testosterone at a dose of 75 mg per day and/or monthly 24'000 IU Vitamin D reduces the fall risk in pre-frail hypogonadal men aged 65 and older. DESIGN: 2 × 2 factorial design randomized controlled trial, follow up of 12 months. METHODS: Hypogonadism was defined as total testosterone <11.3 nmol/L and pre-frailty as ≥1 Fried- frailty criteria and/or being at risk for falling at the time of screening. The primary outcomes were number of fallers and the rate of falls, assessed prospectively. Secondary outcomes were appendicular lean mass (ALM), sit-to-stand, gait speed, and the short physical performance test battery. Analyses were adjusted for age, BMI, fall history and the respective baseline measurement. RESULTS: We aimed to recruit 168 men and stopped at 91 due to unexpected low recruitment rate (1266 men were pre-screened). Mean age was 72.2 years, serum total testosterone was 10.8 ± 3.0 nmol/l, and 20.9% had 25(OH)D levels below 20 ng/mL. Over 12 months, 37 participants had 72 falls. Neither the odds of falling nor the rate of falls were reduced by testosterone or by vitamin D. Testosterone improved ALM compared to no testosterone (0.21 kg/m2 [0.06, 0.37]), and improved gait speed (0.11 m/s, [0.03, 0.20]) compared to placebo. CONCLUSION: Transdermal testosterone did not reduce fall risk but improved ALM and gait speed in pre-frail older men. Monthly vitamin D supplementation had no benefit.

Association Between Multimorbidity and Rate of Falls: A 3-Year 5-Country Prospective Study in Generally Healthy and Active Community-Dwelling Adults Aged ≥70 Years.

OBJECTIVE: To examine the association between the baseline number of chronic diseases and multimorbidity with regard to the incidence of all and injurious falls over 3 years among European community-dwelling older adults. DESIGN: Observational analysis of DO-HEALTH, a double-blind, randomized controlled trial. SETTING AND PARTICIPANTS: Multicenter trial with 7 European centers: Zurich, Basel, Geneva (Switzerland), Berlin (Germany), Innsbruck (Austria), Toulouse (France), and Coimbra (Portugal), including 2157 community-dwelling adults aged 70 years and older without any major health events in the 5 years prior to enrollment, sufficient mobility, and good cognitive status. METHODS: The main outcomes were the number of all falls and injurious falls experienced over 3 years. The number of chronic diseases and multimorbidity, defined as the presence of 3 or more chronic diseases at baseline, were assessed with the Self-Administered Comorbidity Questionnaire by Sangha et al. RESULTS: Among the 2155 participants included in the analyses (mean age: 74.9 years, 62% were women, 52% were physically active more than 3 times a week), 569 (26.4%) had multimorbidity at baseline. Overall, each 1-unit increase in the baseline number of chronic diseases was linearly associated with a 7% increased incidence rate of all falls [adjusted incidence rate ratio (aIRR) 1.07, 95% CI 1.03-1.12, P < .001] and a 6% increased incidence rate of injurious falls (aIRR 1.06, 95% CI 1.02-1.11, P = .003). Baseline multimorbidity was associated with a 21% increased incidence rate of all falls (aIRR 1.21, 95% CI 1.07-1.37, P = .002) and a 17% increased incidence rate of injurious falls (aIRR 1.17, 95% CI 1.03-1.32, P = .02). CONCLUSIONS AND IMPLICATIONS: Baseline number of prevalent chronic diseases and multimorbidity in generally healthy and active community-dwelling older adults were associated with increased incidence rates of all and injurious falls over 3 years. These findings support that multimorbidity may need consideration as a risk factor for falls, even in generally healthy and active older adults.

[Evidence of Physical Training Programs for Fall Prevention in Seniors]. / Evidenz körperlicher Trainings-programme zur Sturzprävention bei älteren Menschen.

Evidence of Physical Training Programs for Fall Prevention in Seniors Abstract. It has been shown that physical exercise reduced fall risk by 23-42% in community-dwelling adults aged 65+. This is particularly true for physical exercises with functional, balance and strength components. Growing evidence shows that functional training is particularly effective in reducing fall risk. Functional training is composed by exercises which reflect activities of daily life, supported by weights and other aids.

Combined Vitamin D, Omega-3 Fatty Acids, and a Simple Home Exercise Program May Reduce Cancer Risk Among Active Adults Aged 70 and Older: A Randomized Clinical Trial.

Objective: The aim of this study was to test the individual and combined benefit of vitamin D, omega-3, and a simple home strength exercise program on the risk of any invasive cancer. Design: The DO-HEALTH trial is a three-year, multicenter, 2 × 2 × 2 factorial design double-blind, randomized-controlled trial to test the individual and combined benefit of three public health interventions. Setting: The trial was conducted between December 2012 and December 2017 in five European countries. Participants: Generally healthy community-dwelling adults ≥70 years were recruited. Interventions: Supplemental 2000 IU/day of vitamin D3, and/or 1 g/day of marine omega-3s, and/or a simple home strength exercise (SHEP) programme compared to placebo and control exercise. Main outcome: In this pre-defined exploratory analysis, time-to-development of any verified invasive cancer was the primary outcome in an adjusted, intent-to-treat analysis. Results: In total, 2,157 participants (mean age 74.9 years; 61.7% women; 40.7% with 25-OH vitamin D below 20 /ml, 83% at least moderately physically active) were randomized. Over a median follow-up of 2.99 years, 81 invasive cancer cases were diagnosed and verified. For the three individual treatments, the adjusted hazard ratios (HRs, 95% CI, cases intervention versus control) were 0.76 (0.49-1.18; 36 vs. 45) for vitamin D3, 0.70 (0.44-1.09, 32 vs. 49) for omega-3s, and 0.74 (0.48-1.15, 35 vs. 46) for SHEP. For combinations of two treatments, adjusted HRs were 0.53 (0.28-1.00; 15 vs. 28 cases) for omega-3s plus vitamin D3; 0.56 (0.30-1.04; 11 vs. 21) for vitamin D3 plus SHEP; and 0.52 (0.28-0.97; 12 vs. 26 cases) for omega-3s plus SHEP. For all three treatments combined, the adjusted HR was 0.39 (0.18-0.85; 4 vs. 12 cases). Conclusion: Supplementation with daily high-dose vitamin D3 plus omega-3s, combined with SHEP, showed cumulative reduction in the cancer risk in generally healthy and active and largely vitamin D-replete adults ≥70 years. Clinical Trial Registration: ClinicalTrials.gov, Identifier: NCT01745263.

Prevalence of polypharmacy in community-dwelling older adults from seven centres in five European countries: a cross-sectional study of DO-HEALTH.

OBJECTIVE: To investigate the prevalence of polypharmacy and characteristics associated with polypharmacy in older adults from seven European cities. DESIGN: Cross-sectional study of baseline data from DO-HEALTH. SETTING AND PARTICIPANTS: DO-HEALTH enrolled 2157 community-dwelling adults age 70 and older from seven centres in Europe. Participants were excluded if they had major health problems or Mini-Mental State Examination Score <24 at baseline. PRIMARY OUTCOME MEASURES: Extensive information on prescription and over-the-counter medications were recorded. Polypharmacy was defined as the concomitant use of five or more medications, excluding vitamins or dietary supplements. Bivariate and multivariable logistic regression was used to test the association of sociodemographic factors (age, sex, years of education, living situation and city) and health-related indicators (number of comorbidities, cognitive function, frailty status, body mass index (BMI), prior fall, self-rated health and smoking status) with polypharmacy. RESULTS: 27.2% of participants reported polypharmacy ranging from 16.4% in Geneva to 60.8% in Coimbra. In the multivariable logistic regression analyses, older age (OR 1.07; 95% CI 1.04 to 1.10), greater BMI (OR 1.09; 95% CI 1.06 to 1.12) and increased number of comorbidities (OR 2.13; 95% CI 1.92 to 2.36) were associated with polypharmacy. Women were less likely to report polypharmacy than men (OR 0.65; 95% CI 0.51 to 0.84). In comparison to participants from Zurich, participants from Coimbra were more likely to report polypharmacy (OR 2.36; 95% CI 1.56 to 3.55), while participants from Geneva or Toulouse were less likely to report polypharmacy ((OR 0.36; 95% CI 0.22 to 0.59 and OR 0.64; 95% CI 0.42 to 0.96), respectively). Living situation, smoking status, years of education, prior fall, cognitive function, self-rated health and frailty status were not significantly associated with polypharmacy. CONCLUSION: Polypharmacy is common among relatively healthy older adults, with moderate variability across seven European cities. Independent of several confounders, being a woman, older age, greater BMI and greater number of comorbidities were associated with increased odds for polypharmacy. TRIAL REGISTRATION NUMBER: NCT01745263.

Effects of vitamin D, omega-3 fatty acids, and a simple home strength exercise program on fall prevention: the DO-HEALTH randomized clinical trial.

BACKGROUND: The roles of vitamin D, omega-3 fatty acids, and home exercise on fall prevention among generally healthy and active older adults are unclear. OBJECTIVES: We tested the effects of daily supplemental vitamin D, daily supplemental marine omega-3s fatty acids, and a simple home exercise program (SHEP), alone or in combination, on the incidences of total and injurious falls among generally healthy older adults. METHODS: We performed a 2 × 2 × 2 factorial-design randomized controlled trial among 2157 community-dwelling adults aged 70 years and older, who had no major health events in the 5 years prior to enrolment, recruited from Switzerland, Germany, Austria, France, and Portugal between December 2012 and November 2014. Participants were randomly assigned to supplementation with 2000 international units/day of vitamin D3 and/or 1 g/day of marine omega-3s, and/or a SHEP compared with placebo and/or control exercise over 3 years. The primary endpoint for the present fall analysis was the incidence rate of total falls. Falls were recorded prospectively throughout the trial. Since there were no interactions between treatments, the main effects are reported based on a modified intent-to-treat analysis. RESULTS: Of 2157 randomized participants, 1900 (88%) completed the study. The mean age was 74.9 years, 61.7% were women, 40.7% had a serum 25-hydroxyvitamin D concentration < 20 ng/ml, and 83% were at least moderately physically active. In total, 3333 falls were recorded over a median follow-up of 2.99 years. Overall, vitamin D and the SHEP had no benefit on total falls, whilst supplementation with omega-3s compared to no omega-3 supplementation reduced total falls by 10% (incidence rate ratio = 0.90; 95% CI, 0.81-1.00; P = 0.04). CONCLUSIONS: Among generally healthy, active, and vitamin D-replete older adults, omega-3 supplementation may have a modest benefit on the incidence of total falls, whilst a daily high dose of vitamin D or a SHEP had no benefit.

DO-HEALTH: Vitamin D3 - Omega-3 - Home exercise - Healthy aging and longevity trial - Design of a multinational clinical trial on healthy aging among European seniors.

DO-HEALTH is a multi-center clinical trial among 2157 community-dwelling European men and women age 70 and older. The 2x2x2 randomized-control factorial design trial tested the individual and additive benefit, as well as the cost-effectiveness, of 3 interventions: vitamin D 2000 IU/day, omega-3 fatty acids 1000 mg/day (EPA + DHA, ratio 1:2), and a 30-minute 3 times/week home exercise (strength versus flexibility). Each treatment tested has shown considerable prior promise from mechanistic studies, small clinical trials, or large cohort studies, in the prevention of common age-related chronic diseases, but definitive data are missing. DO-HEALTH will test these interventions in relation to 6 primary endpoints (systolic and diastolic blood pressure, non-vertebral fractures, Short Physical Performance Battery score, the Montreal Cognitive Assessment, and risk of infections), plus several secondary endpoints explored in ancillary studies (i.e. rate of any falls and injurious falls, joint pain, oral health, quality of life, and incident frailty). As the 3 interventions have distinct mechanisms of action for each of the 6 primary endpoints, a maximum benefit is expected for their additive benefit as a "multi-modal" intervention. The trial duration is 3 years with in-person contacts with all participants at 4 clinical visits and by quarterly phone calls. Baseline and follow-up blood samples were collected in all participants to measure changes in 25-hydroxyvitamin D and poly-unsaturated fatty acid concentrations. Our objective was to test interventions that are expected to promote healthy aging and longer life expectancy and that can be easily and safely implemented by older community-dwelling adults.

Effect of Vitamin D Supplementation, Omega-3 Fatty Acid Supplementation, or a Strength-Training Exercise Program on Clinical Outcomes in Older Adults: The DO-HEALTH Randomized Clinical Trial.

Importance: The benefits of vitamin D, omega-3 fatty acids, and exercise in disease prevention remain unclear. Objective: To test whether vitamin D, omega-3s, and a strength-training exercise program, alone or in combination, improved 6 health outcomes among older adults. Design, Setting, and Participants: Double-blind, placebo-controlled, 2 × 2 × 2 factorial randomized clinical trial among 2157 adults aged 70 years or older who had no major health events in the 5 years prior to enrollment and had sufficient mobility and good cognitive status. Patients were recruited between December 2012 and November 2014, and final follow-up was in November 2017. Interventions: Participants were randomized to 3 years of intervention in 1 of the following 8 groups: 2000 IU/d of vitamin D3, 1 g/d of omega-3s, and a strength-training exercise program (n = 264); vitamin D3 and omega-3s (n = 265); vitamin D3 and exercise (n = 275); vitamin D3 alone (n = 272); omega-3s and exercise (n = 275); omega-3s alone (n = 269); exercise alone (n = 267); or placebo (n = 270). Main Outcomes and Measures: The 6 primary outcomes were change in systolic and diastolic blood pressure (BP), Short Physical Performance Battery (SPPB), Montreal Cognitive Assessment (MoCA), and incidence rates (IRs) of nonvertebral fractures and infections over 3 years. Based on multiple comparisons of 6 primary end points, 99% confidence intervals are presented and P < .01 was required for statistical significance. Results: Among 2157 randomized participants (mean age, 74.9 years; 61.7% women), 1900 (88%) completed the study. Median follow-up was 2.99 years. Overall, there were no statistically significant benefits of any intervention individually or in combination for the 6 end points at 3 years. For instance, the differences in mean change in systolic BP with vitamin D vs no vitamin D and with omega-3s vs no omega-3s were both -0.8 (99% CI, -2.1 to 0.5) mm Hg, with P < .13 and P < .11, respectively; the difference in mean change in diastolic BP with omega-3s vs no omega-3s was -0.5 (99% CI, -1.2 to 0.2) mm Hg; P = .06); and the difference in mean change in IR of infections with omega-3s vs no omega-3s was -0.13 (99% CI, -0.23 to -0.03), with an IR ratio of 0.89 (99% CI, 0.78-1.01; P = .02). No effects were found on the outcomes of SPPB, MoCA, and incidence of nonvertebral fractures). A total of 25 deaths were reported, with similar numbers in all treatment groups. Conclusions and Relevance: Among adults without major comorbidities aged 70 years or older, treatment with vitamin D3, omega-3s, or a strength-training exercise program did not result in statistically significant differences in improvement in systolic or diastolic blood pressure, nonvertebral fractures, physical performance, infection rates, or cognitive function. These findings do not support the effectiveness of these 3 interventions for these clinical outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT01745263.

Outcomes after spinal stenosis surgery by type of surgery in adults aged 60 years and older.

AIMS OF THE STUDY: Mobility disability due to spinal stenosis is common in the senior population and often surgery is warranted for patients with severe symptoms and neurological dysfunction. However, although current clinical guidelines recommend stabilisation surgery in addition to decompression in patients with spinal stenosis and instability due to degenerative spondylolisthesis, the relationship between outcomes and the specific type of surgery have not been well studied. We therefore assessed the postoperative recovery timeline for 12 months and compared patient-reported outcomes dependent on the extent of decompression and additional stabilisation among seniors undergoing spinal stenosis surgery. METHODS: We investigated 457 patients (mean age 76.0 ± 10.7 years, 58% women) from a consecutive cohort prior to spinal stenosis surgery. Follow-up was at 3 or 6months and at 12 months postoperatively. At each visit, pain, neurological dysfunction and disability were assessed using the North American Spine Society questionnaire. Repeated-measures analysis compared outcomes by type of surgery adjusting for baseline symptoms, gender, age, number of comorbidities, centre and year of surgery. RESULTS: Most improvement occurred within the first 3 to 6 months with little or no further improvement at 12 months. Over 12 months and in adjusted models, patients receiving one-segment versus multi-segment decompression experienced significantly greater reduction of pain (−49.2% vs −41.9%, p = 0.013) and neurological dysfunction (−37.1% vs −25.9%, p <0.0001), but only borderline greater reduction of disability (−32.7% vs −28.2%, p = 0.051). Moreover, reduction in pain and neurological function did not differ with or without additional stabilisation and extend of decompression. However, patients who received one-segment (−28.9%) or multi-segment (−28.3%) stabilisation experienced significantly less reduction in disability after surgery compared with those who were not stabilised (−34.1%, p <0.043). CONCLUSIONS: Among senior patients undergoing spinal stenosis surgery, recovery was largely complete by 3 to 6 months after surgery and differed little by type of surgery independently of symptoms prior to surgery and other covariates. However we could document a trend toward more improvement in particularly neurological dysfunction and disability with less invasive surgery.

Effect of daily 2000 IU versus 800 IU vitamin D on blood pressure among adults age 60 years and older: a randomized clinical trial.

BACKGROUND: Observational studies report higher blood pressure (BP) among individuals with lower 25-hydroxyvitamin D concentration. Whether dosage of vitamin D supplementation has a differential effect on BP control remains unclear. OBJECTIVE: The study aimed to determine if daily vitamin D supplementation with 2000 IU is more effective than 800 IU for BP control among older adults. METHODS: This randomized, double-blind, ancillary trial of the Zurich Multiple Endpoint Vitamin D Trial in Knee Osteoarthritis enrolled adults aged ≥60 y who underwent elective surgery due to severe knee osteoarthritis. Participants were randomly assigned to receive high dose (2000 IU) or standard dose (800 IU) daily vitamin D3 for 24 mo. Outcomes included daytime and 24-h mean systolic BP. BP variability and serum 25-hydroxyvitamin D concentration were examined in a post hoc and observational analysis. RESULTS: Of the 273 participants randomly assigned, 250 participants completed a follow-up 24-h ambulatory BP monitoring (mean age: 70.4 ± 6.4 y; 47.2% men). The difference in daytime mean systolic BP reduction between the 2000 IU (n = 123) and 800 IU (n = 127) groups was not statistically significant (-2.75 mm Hg vs. -3.94 mm Hg; difference: 1.18 mm Hg; 95% CI: -0.68, 3.05; P = 0.21), consistent with 24-h mean systolic BP. However, systolic BP variability was significantly reduced with 2000 IU (average real variability: -0.37 mm Hg) compared to 800 IU vitamin D3 (0.11 mm Hg; difference: -0.48 mm Hg; 95% CI: -0.94, -0.01; P = 0.045). Independent of group allocation, maximal reductions in mean BP were observed at 28.7 ng/mL of achieved serum 25-hydroxyvitamin D concentrations. CONCLUSIONS: While daily 2000 IU and 800 IU vitamin D3 reduced mean systolic BP over 2 y to a small and similar extent, 2000 IU reduced mean systolic BP variability significantly more compared with 800 IU. However, without a placebo control group we cannot ascertain whether vitamin D supplementation effectively reduces BP.This trial was registered at www.clinicaltrials.gov as NCT00599807.

Comparative Effectiveness of Functional Tests in Fall Prediction After Hip Fracture.

OBJECTIVES: To assess the validity of 4 functional tests in predicting falls within the first year after hip fracture. DESIGN: Prospective study of functional tests shortly after hip surgery and incident falls during 12 months' follow-up. SETTING AND PARTICIPANTS: The sample comprised 173 adults with acute hip fracture, aged 65 years and older (79% women, 77% community dwelling, mean age 84.2 years), who participated in a clinical trial of vitamin D or home exercise. METHODS: We assessed 4 functional tests [Timed Up and Go test (TUG), grip strength, and knee flexor and extensor strength in the nonoperated leg] by trained study physiotherapists at baseline (1-12 days after hip fracture surgery). During 12 months' follow-up, we ascertained all fall events by monthly personal phone calls, a telephone hotline, and a patient diary. Then we compared TUG and strength test performance at baseline between future single fallers, recurrent fallers, and nonfallers over the 12-month follow-up. All analyses adjusted for age, body mass index, gender, 25-hydroxyvitamin D status at baseline, days of follow-up, and treatment allocation (the original trial tested vitamin D treatment and/or a home exercise program). RESULTS: Ninety-two of 173 (53%) participants fell and experienced 212 falls. Participants who became recurrent fallers (n = 54) had significantly longer TUG times at baseline than those who did not fall (n = 81) in the following 12 months (mean TUG for recurrent fallers = 71.6 seconds, SD = 8.2 seconds, vs mean TUG for nonfallers = 51.4 seconds, SD = 6.9 seconds; P = .02). There were no significant differences in TUG times between single fallers and nonfallers. For all 3 strength tests, there were no significant differences between single fallers, recurrent fallers, and nonfallers. CONCLUSIONS AND IMPLICATIONS: In this population of frail older adults recruited shortly after hip fracture surgery, only the TUG test discriminated between future recurrent fallers and nonfallers over a 12-month follow-up. Because of the high incidence and serious consequences of falls in older adults after a hip fracture, it is very important to identify practical and clinically related tests to predict repeated falls in the first year after a hip fracture, which is of great public health importance.

Total Serum Testosterone and Western Ontario and McMaster Universities Osteoarthritis Index Pain and Function Among Older Men and Women With Severe Knee Osteoarthritis.

OBJECTIVE: To investigate whether serum total testosterone level is associated with knee pain and function in men and women with severe knee osteoarthritis (OA). METHODS: We enrolled 272 adults age ≥60 years (mean ± SD age 70.4 ± 4.4 years, 53% women) who underwent unilateral total knee replacement (TKR) due to severe knee OA. Serum testosterone levels and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and function of the operated and contralateral knee were measured at 6-8 weeks after surgery. At the nonoperated knee, 56% of participants had radiographic knee OA with a Kellgren/Lawrence grade ≥2. Cross-sectional analyses were performed by sex and body mass index (BMI) subgroups, using multivariable regression adjusted for age, physical activity, and BMI. RESULTS: At the operated knee, higher testosterone levels were associated with less WOMAC pain in men (B = -0.62, P = 0.046) and women (B = -3.79, P = 0.02), and less WOMAC disability scores in women (B = -3.62, P = 0.02) and obese men (B = -1.99, P = 0.02). At the nonoperated knee, testosterone levels were not associated with WOMAC pain in men or women, but higher testosterone levels were associated with less disability in women (B = -0.95, P = 0.02). Testosterone levels were inconsistently associated with pain and disability in BMI subgroups among men. Only among obese women, testosterone levels were inversely associated with radiographic knee OA (odds ratio = 0.10, P = 0.003). CONCLUSION: Higher total testosterone levels were associated with less pain in the operated knee in men and women undergoing TKR and less disability in women. At the nonoperated knee, higher testosterone levels were inconsistently associated with less pain and disability.

Polypharmacy and Kidney Function in Community-Dwelling Adults Age 60 Years and Older: A Prospective Observational Study.

OBJECTIVES: Information on the impact of polypharmacy on kidney function in older adults is limited. We prospectively investigated the association between intake of total number of drugs or nonsteroidal anti-inflammatory drugs (NSAIDs) and kidney function. DESIGN: Our study is a prospective observational analysis of the 2-year Zurich Multiple Endpoint Vitamin D Trial in Knee Osteoarthritis Patients. SETTING AND PARTICIPANTS: Of the 273 participants of the original trial, 270 participants (mean age 70.3 ± 6.4 years, 53% women) were included in this observational analysis. METHODS: The associations between (1) total number of drugs (or NSAIDs) at baseline or (2) cumulative number of drugs (or NASAIDs) repeatedly measured over 24 months and kidney function repeatedly measured over 24 months as estimated glomerular filtration rate (eGFR) were investigated using multivariable-adjusted repeated-measures analysis. RESULTS: Per drug at baseline, kidney function decreased by 0.64 mL/min/1.73 m2 eGFR (Beta = -0.64; 95% CI -1.19 to -0.08; P = .024) over 24 months. With every additional drug taken cumulatively over 24 months, kidney function decreased by 0.39 mL/min/1.73 m2 eGFR (Beta = -0.39; 95% CI -0.63 to -0.15; P = .002). In a high-risk subgroup, per NSAID taken cumulatively over 24 months, kidney function declined by 1.21 mL/min/1.73 m2 eGFR (Beta = -1.21; 95% CI -2.35 to -0.07; P = .021). CONCLUSIONS AND IMPLICATIONS: For every additional drug prescribed among older adults, our study supports an independent and immediate harmful impact on kidney function. This negative impact seems to be about 3 times greater for NSAIDs compared with an additional average drug.

Effect of Monthly High-Dose Vitamin D on Mental Health in Older Adults: Secondary Analysis of a RCT.

OBJECTIVES: To test the effect of monthly high-dose vitamin D supplementation on mental health in pre-frail older adults. DESIGN: Ancillary study of a 1-year double-blind randomized clinical trial conducted in Zurich, Switzerland. SETTING AND PARTICIPANTS: A total of 200 community-dwelling adults 70 years and older with a prior fall event in the last year. Participants were randomized to receive 24 000 IU vitamin D3 (considered standard of care), 60 000 IU vitamin D3 , or 24 000 IU vitamin D3 plus 300 µg calcifediol per month. MEASURES: The primary end point was the Mental Component Summary (MCS) of the SF-36. Secondary end points were the SF-36 Mental Health (MH) subscale and the Geriatric Depression Scale (GDS-15). RESULTS: Participants' mean age was 78 years (67% women), and 58% were vitamin D deficient (<20 ng/mL). Over time, primary and secondary end points did not differ significantly among the three treatment groups or in subgroups by vitamin D status at baseline. Given the lack of a true placebo group, we explored in a predefined observational analysis the change in mental health scales by achieved 25(OH)D levels at 12 months. After adjusting for confounders, participants achieving the highest 25(OH)D quartile (Q) at 12 months (44.7-98.9 ng/mL) had the greatest improvements in MCS (Q4 = 0.79 vs Q1 = -2.9; p = .03) and MH scales (Q4 = 2.54 vs Q1 = -3.07; p = .03); these associations were strongest among participants who were vitamin D deficient at baseline. No association was found for GDS (p = .89). CONCLUSIONS: For mental health, our study suggests no benefit of higher monthly doses of vitamin D3 compared with the standard monthly dose of 24 000 IU. However, irrespective of vitamin D treatment dose, achieving higher 25(OH)D levels at 12-month follow-up was associated with a small, clinically uncertain but statistically significant improvement in mental health scores.

Effect of Monthly Vitamin D on Chronic Pain Among Community-Dwelling Seniors: A Randomized, Double-Blind Controlled Trial.

OBJECTIVE: With advancing age, the prevalence of vitamin D deficiency and musculoskeletal pain increases. However, published data on the effectiveness of vitamin D supplementation in reducing chronic pain are inconclusive. The purpose of this study was to test the effect of 3 different monthly doses of vitamin D on chronic pain in seniors 70 years and older with a prior fall event. DESIGN: 1-year, double-blind randomized clinical trial. SETTING: The trial was conducted in Zurich, Switzerland. Participants were 200 community-dwelling men and women 70 years and older with a prior fall. INTERVENTION: Three study groups with monthly treatments were randomized to either a low-dose control group of vitamin D (24,000 IU vitamin D3/mo), a high dose of vitamin D3 (60,000 IU vitamin D3/mo), or a combination of calcifediol and vitamin D3 (24,000 IU vitamin D3 plus 300 µg calcifediol/mo). MEASUREMENTS: The primary endpoint was the change in the mean number of painful areas using the McGill Pain map over 12 months of follow-up. All analyses were adjusted for age, sex, body mass index, 25-hydroxyvitamin (OH)D3 levels, and pain scores at baseline. A predefined subgroup analysis was performed by baseline 25(OH)D status (<20 vs ≥ 20 ng/mL). RESULTS: The mean age of the participants was 78 years, 67.0% (134 of 200) were female, and 58.0% (116 of 200) were vitamin D deficient (<20 ng/mL) at baseline. Over 12 months of follow-up, the changes in the mean number of painful areas did not differ significantly among treatment groups (P = .46). However, there was a significant interaction effect between baseline vitamin levels (<20 vs ≥ 20 ng/mL) and treatment (P = .02). Among those who were vitamin D replete at baseline (n = 84), there was a significant difference between treatment groups over time (P = .04), and only seniors in the 24,000-IU vitamin D3 group had a marginally significant decrease in their total mean pain score (-0.77; 95% CI, -1.56 to 0.01, P = .05), whereas there were no changes in the high-dose groups. Among seniors who were vitamin D deficient at baseline (n = 116), chronic pain did not differ by treatment groups over time (P = .33). CONCLUSION: Our results suggest that both starting level of 25(OH)D3 and monthly treatment dose of vitamin D may be important with respect to chronic pain reduction-with the only benefit seen among vitamin D-replete seniors treated with a monthly dose of 24,000 IU vitamin D3.

Effect of 800 IU Versus 2000 IU Vitamin D3 With or Without a Simple Home Exercise Program on Functional Recovery After Hip Fracture: A Randomized Controlled Trial.

OBJECTIVES: To evaluate 2 simple strategies, vitamin D3 and a home exercise program, in functional recovery during the first year after hip fracture. DESIGN: Secondary analysis of a factorial clinical trial. Patients were randomly allocated to 800 IU (standard of care) or 2000 IU vitamin D3 and a daily instruction of a simple home exercise program (SHEP) or standard physiotherapy alone during acute care. SETTING AND PARTICIPANTS: Acute hip fracture patients aged ≥65 years, after hip fracture surgery, admitted to a large hospital in Zurich, Switzerland. MEASURES: Three objective measures of lower extremity function were assessed at baseline and 6 and 12 months, with the Timed Up and Go test (TUG) as the primary endpoint, and knee flexor and extensor strength, and a self-reported physical function score (PF-10) as secondary endpoints. Linear mixed model regression analyses were based on intention to treat, adjusting for baseline function, time, age, sex, and baseline 25-hydroxyvitamin D level. RESULTS: We enrolled 173 patients (79.2% women; mean age 84 years; 77.5% living at home). A significant interaction was found between vitamin D3 dose and SHEP for TUG (P = .045). Thus, findings compared the standard of care reference arm with 800 IU vitamin D3 without SHEP to 3 interventions arms (800 IU vitamin D3+SHEP; 2000 IU vitamin D3 without SHEP; 2000 IU vitamin D3+SHEP). For TUG, over 12 months the 800 IU vitamin D3+SHEP group performed significantly better than the standard-of-care group (13.8 vs 19.5 seconds; P = .01). Findings for knee flexor strength were in line with TUG results and approached significance (P = .07), whereas knee extensor strength and PF-10 did not differ by treatments. CONCLUSIONS/IMPLICATIONS: For functional recovery after hip fracture, combining home exercise with 800 IU vitamin D3 is superior to no home exercise or 2000 IU vitamin D3. None of the interventions improved subjective physical functioning.

Recovery after unilateral knee replacement due to severe osteoarthritis and progression in the contralateral knee: a randomised clinical trial comparing daily 2000 IU versus 800 IU vitamin D.

OBJECTIVE: To test whether daily high-dose vitamin D improves recovery after unilateral total knee replacement. METHODS: Data come from a 24-month randomised, double-blind clinical trial. Adults aged 60 and older undergoing unilateral joint replacement due to severe knee osteoarthritis were 6-8 weeks after surgery randomly assigned to receive daily high-dose (2000 IU) or standard-dose (800 IU) vitamin D3. The primary endpoints were symptoms (Western Ontario and McMaster Universities Arthritis Index pain and function scores) assessed at baseline, 6, 12, 18 and 24 months in both knees, and the rate of falls over 24 months. The secondary outcomes were sit-to-stand performance, gait speed, physical activity and radiographic progression in the contralateral knee. RESULTS: We recruited 273 participants, 137 were randomised to receive 2000 IU and 136 were randomised to receive 800 IU vitamin D per day. 2000 IU vitamin D increased 25-hydroxyvitamin D levels to 45.6 ng/mL and 800 IU vitamin D to 37.1 ng/mL at month 24 (p<0.0001). While symptoms improved significantly in the operated knee and remained stable in the contralateral knee over time, none of the primary or secondary endpoints differed by treatment group over time. The rate of falls over 24 months was 1.05 with 2000 IU and 1.07 with 800 IU (p=0.84). 30.5% of participants in the 2000 IU and 31.3% of participants in the 800 IU group had radiographic progression in the contralateral knee over 24 months (p=0.88). CONCLUSIONS: Our findings suggest that a 24-month treatment with daily 2000 IU vitamin D did not show greater benefits or harm than a daily standard dose of 800 IU among older adults undergoing unilateral total knee replacement.