Monthly High-Dose Vitamin D Treatment for the Prevention of Functional Decline: A Randomized Clinical Trial.

IMPORTANCE: Vitamin D deficiency has been associated with poor physical performance. OBJECTIVE: To determine the effectiveness of high-dose vitamin D in lowering the risk of functional decline. DESIGN, SETTING, AND PARTICIPANTS: One-year, double-blind, randomized clinical trial conducted in Zurich, Switzerland. The screening phase was December 1, 2009, to May 31, 2010, and the last study visit was in May 2011. The dates of our analysis were June 15, 2012, to October 10, 2015. Participants were 200 community-dwelling men and women 70 years and older with a prior fall. INTERVENTIONS: Three study groups with monthly treatments, including a low-dose control group receiving 24,000 IU of vitamin D3 (24,000 IU group), a group receiving 60,000 IU of vitamin D3 (60,000 IU group), and a group receiving 24,000 IU of vitamin D3 plus 300 µg of calcifediol (24,000 IU plus calcifediol group). MAIN OUTCOMES AND MEASURES: The primary end point was improving lower extremity function (on the Short Physical Performance Battery) and achieving 25-hydroxyvitamin D levels of at least 30 ng/mL at 6 and 12 months. A secondary end point was monthly reported falls. Analyses were adjusted for age, sex, and body mass index. RESULTS: The study cohort comprised 200 participants (men and women ≥ 70 years with a prior fall). Their mean age 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. Intent-to-treat analyses showed that, while 60,000 IU and 24,000 IU plus calcifediol were more likely than 24,000 IU to result in 25-hydroxyvitamin D levels of at least 30 ng/mL (P = .001), they were not more effective in improving lower extremity function, which did not differ among the treatment groups (P = .26). However, over the 12-month follow-up, the incidence of falls differed significantly among the treatment groups, with higher incidences in the 60,000 IU group (66.9%; 95% CI, 54.4% to 77.5%) and the 24,000 IU plus calcifediol group (66.1%; 95% CI, 53.5%-76.8%) group compared with the 24,000 IU group (47.9%; 95% CI, 35.8%-60.3%) (P = .048). Consistent with the incidence of falls, the mean number of falls differed marginally by treatment group. The 60,000 IU group (mean, 1.47) and the 24,000 IU plus calcifediol group (mean, 1.24) had higher mean numbers of falls compared with the 24,000 IU group (mean, 0.94) (P = .09). CONCLUSIONS AND RELEVANCE: Although higher monthly doses of vitamin D were effective in reaching a threshold of at least 30 ng/mL of 25-hydroxyvitamin D, they had no benefit on lower extremity function and were associated with increased risk of falls compared with 24,000 IU. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01017354.

The value of serum procalcitonin level for differentiation of infectious from noninfectious causes of fever after orthopaedic surgery.

BACKGROUND: Early diagnosis of postoperative orthopaedic infections is important in order to rapidly initiate adequate antimicrobial therapy. There are currently no reliable diagnostic markers to differentiate infectious from noninfectious causes of postoperative fever. We investigated the value of the serum procalcitonin level in febrile patients after orthopaedic surgery. METHODS: We prospectively evaluated 103 consecutive patients with new onset of fever within ten days after orthopaedic surgery. Fever episodes were classified by two independent investigators who were blinded to procalcitonin results as infectious or noninfectious origin. White blood-cell count, C-reactive protein level, and procalcitonin level were assessed on days 0, 1, and 3 of the postoperative fever. RESULTS: Infection was diagnosed in forty-five (44%) of 103 patients and involved the respiratory tract (eighteen patients), urinary tract (eighteen), joints (four), surgical site (two), bloodstream (two), and soft tissues (one). Unlike C-reactive protein levels and white blood-cell counts, procalcitonin values were significantly higher in patients with infection compared with patients without infection on the day of fever onset (p = 0.04), day 1 (p = 0.07), and day 3 (p = 0.003). Receiver-operating characteristics demonstrated that procalcitonin had the highest diagnostic accuracy, with a value of 0.62, 0.62, and 0.71 on days 0, 1, and 3, respectively. In a multivariate logistic regression analysis, procalcitonin was a significant predictor for postoperative infection on days 0, 1, and 3 of fever with an odds ratio of 2.3 (95% confidence interval, 1.1 to 4.4), 2.3 (95% confidence interval, 1.1 to 5.2), and 3.3 (95% confidence interval, 1.2 to 9.0), respectively. CONCLUSIONS: Serum procalcitonin is a helpful diagnostic marker supporting clinical and microbiological findings for more reliable differentiation of infectious from noninfectious causes of fever after orthopaedic surgery.

Nonmodular flexible press-fit cup in primary total hip arthroplasty: 15-year followup.

The key rationale for a nonmodular flexible press-fit cup was to maximize long-term stability with a cementless, porous metal-coated cup that is low in stiffness (no metal shell) and to achieve fixation solely through biradial eccentricity between the cup and the acetabular cavity. We asked whether the promising results achieved at 5 and 10 years would be maintained at 15 years. We reviewed 261 patients who received the first 280 Morscher Press-Fit Cups. One hundred twenty patients (126 hips) died. One hundred one patients (112 hips) had a clinical and radiographic followup after a minimum of 13.5 years (mean, 14.7 years; range, 13.5-17.0 years). Twenty-four patients with 26 hips were clinically examined or interviewed by telephone. Three of the 101 patients were lost to followup. We judged the results excellent or good in 96% of the hips. The 15-year overall survivorship was 95.3% and with the end point of aseptic loosening, the survivorship was 97.5%. Wear was greater in cups with an inclination greater than 45 degrees and in metal-polyethylene pairings compared with ceramic-polyethylene pairings. This cup design performs well over the long term.

Muscular lower leg asymmetry in middle-aged people.

BACKGROUND: The purpose of this study was to determine whether muscular asymmetries were present in the lower legs of recreationally active middle-aged people grouped by leg dominance. METHODS: Twelve healthy middle-aged subjects were analyzed bilaterally. The clinical variables included leg dominance, sports level, range of motion, lower leg alignment, calf circumference, and AOFAS (American Orthopaedic Foot and Ankle Society) ankle score. The biomechanical variables included maximal voluntary isometric ankle joint torque and surface electromyography (EMG) with determination of mean EMG frequency and intensity of four lower leg muscles: anterior tibial (AT), medial gastrocnemius (MG), soleus (SO), and peroneus longus (PL). RESULTS: The mean EMG frequency was significantly lower in the dominant leg for the AT (dominant, 148.6 Hz; nondominant, 157.8 Hz) and MG muscles (dominant, 183.9 Hz; nondominant, 196.8 Hz). A significantly higher plantarflexion torque was found in the dominant leg (27.1 Nm) compared to the nondominant leg (22.9 Nm). Higher (not significant) dorsiflexion torque was found in the dominant leg (dominant, 27.3 Nm; nondominant, 24.8 Nm). The calf circumference was marginally significantly higher (p =0.039) in the dominant leg (34.2 cm; nondominant leg, 33.8 cm). The dominant leg had a higher but not significantly different mean EMG intensity for all four muscles. CONCLUSIONS AND CLINICAL RELEVANCE: Differences in muscle EMG and torque were found between the dominant and nondominant lower leg. These results might be applicable to treatment, rehabilitation, and future research of lower leg and foot and ankle disorders.

Scandinavian total ankle replacement: a 3.7-year average followup of 65 patients.

The purpose of the current prospective study was to determine the midterm results of 68 total ankle replacements with the Scandinavian Total Ankle Replacement (S.T.A.R.) prosthesis. The 65 patients (34 women and 31 men; mean age at surgery, 56.1 years [range, 22-85 years]) were assessed clinically and radiologically after 3.7 years (range, 2.4-6.2 years). Thirty-five patients (54%) were totally pain-free. The overall clinical score was graded as excellent or good in 67 ankles. The American Orthopaedic Foot and Ankle Society hindfoot score improved from 24.7 points (range, 3-44 points) preoperatively to 84.3 points (range, 44-100 points) at followup. Three patients (three ankles, 4.4%) had a ballooning bone lysis on the tibial side. Despite prophylaxis, periarticular hypertrophic bone formation was seen in 43 ankles (63%; 42 patients), associated with a decrease of dorsiflexion and plantar flexion. Nine ankles (13%; nine patients) had revision surgery because of problems with the components and 14 ankles (21%; 14 patients) had secondary or additional operations. All revision or secondary surgeries were successful, and no ankle had to be converted to an ankle arthrodesis. The early experience with the S.T.A.R. ankle implant is encouraging, although we have encountered more complications and potential problems than previously reported.

The HINTEGRA ankle: rationale and short-term results of 122 consecutive ankles.

The HINTEGRA ankle was developed as an attempt to specifically address the needs of minimal bone resection, extended bone support, proper ligament balancing, and minimal contact stresses within and around the prosthesis. The purpose of this study was to determine the short-term results in a consecutive series of 116 patients (122 ankles). Preoperative diagnoses were posttraumatic osteoarthrosis in 91 ankles (75%), primary osteoarthrosis in 16 ankles (13%), and systemic arthritis in 15 ankles (12%). Eight ankles had to be revised. Four were revised because of loosening of at least one component; one because of dislocation of the meniscus; and three for other reasons. All revisions were successful. After an average of 18.9 months (range, 1-3 years), 84% of patients were satisfied, and the clinical result was rated as good or excellent in 82% of the cases. The American Orthopaedic Foot and Ankle Society hindfoot score improved from 40 points preoperatively to 85 points at followup. Eighty-three ankles (68%) were completely pain-free. The average range of motion clinically was 39 degrees (range, 15 degrees-55 degrees) and under fluoroscopy (true ankle motion) it was 37 degrees (range, 7 degrees-62 degrees). Radiographically, the tibial component was stable in all ankles, and no tilting of the component occurred since surgery. However, migration of the talar component was observed in two ankles. The concept of minimal bone resection and wide bony support was shown to be successful on the tibial and talar sides. Obtained function, pain relief, and patient satisfaction were promising and, compared with other devices, the results mostly were superior. This may support the idea that anatomic-shaped surfaces, as is the case in the HINTEGRA ankle, may be successful in total ankle replacement.

Recovery of the posterior tibial muscle after late reconstruction following tendon rupture.

The purpose of this study was to determine the recovery potential of the posterior tibial muscle after late reconstruction following tendon rupture in stage II of posterior tibial tendon dysfunction. Fourteen patients (18 women, 6 men; mean age 59.8 years) were investigated 47 months (range, 24-76 months) after surgical reconstruction of a completely ruptured posterior tibial tendon (end-to-end anastomosis, side-to-side augmentation with the flexor digitorum longus tendon) in combination with a distal calcaneal osteotomy with a tricortical iliac crest bone graft for lengthening of the lateral column. At follow-up, clinical and radiological investigations were performed, including strength measurement and qualitative and quantitative MRI investigation. The overall clinical results were graded excellent in 12 patients, good in one, fair in one, and poor in none. The average ankle-hindfoot score (American Orthopaedic Foot and Ankle Society) improved from preoperatively 49.1 (range, 32-60) to 93.1 (range, 76-100) at follow-up. The functional result correlated with patient's satisfaction and sports activities (p <.05). All patients showed a significant strength of the posterior tibial muscle on the affected side, but it was smaller than on non-affected side (p <.05). The mean posterior tibial muscle strength was 75.1 N on affected and 104.9 N on nonaffected side, corresponding to a ratio of 0.73 between the two legs. The mean area of the posterior tibial muscle was 1.89 cm(2) on affected side, and 3.48 cm(2) on nonaffected side, corresponding to a ratio of 0.55 between the two legs. While fatty degeneration for the posterior tibial muscle was found in all patients, it was found to decrease with increasing strength of the posterior tibial muscle (p <.05) and muscular size (p <.05). On postoperative MRI, the posterior tibial tendon could be found to be intact in all patients. The recovery potential of the posterior tibial muscle was shown to be significant even after delayed repair of its ruptured tendon. A ruptured and/or diseased posterior tibial tendon should not be transected as it excludes any recovery possibilities of the posterior tibial muscle.

Medial ankle instability: an exploratory, prospective study of fifty-two cases.

BACKGROUND: Very little objective data are available regarding medial ankle instability. HYPOTHESIS: Several structures contribute to the stabilization of the medial ankle, and, in the case of injury, they are not involved in a uniform way. STUDY DESIGN: Explorative, prospective case series. METHODS: Fifty-one patients (52 ankles; males 27, females 25; age 36.4 [16 to 60] years) were surgically treated because of medial ankle instability. All clinical findings and structural changes, as found by arthroscopy and surgical exploration, were compared with the clinical diagnosis and then addressed for surgical reconstruction. RESULTS: Pain in the medial gutter was noted in all ankles (100%). Arthroscopy verified a clinically expected additional lateral instability in 40 ankles (77%). At 4.43 years (2 to 6.5 years) after surgical reconstruction, the clinical result was considered to be good/excellent in 46 cases (90%), fair in 4 cases (8%), and poor in 1 case (2%). CONCLUSION: The clinical characteristics of medial ankle instability are a feeling of giving way, pain on the medial gutter of the ankle, and a valgus and pronation deformity of the foot that can typically be actively corrected by the posterior tibial muscle. Arthroscopy was shown to be a very helpful diagnostic tool in verifying medial instability.

Identifying a cut-off point for normal mobility: a comparison of the timed 'up and go' test in community-dwelling and institutionalised elderly women.

BACKGROUND: physical mobility testing is an essential component of the geriatric assessment. The timed up and go test measures basic mobility skills including a sequence of functional manoeuvres used in everyday life. OBJECTIVES: to create a practical cut-off value to indicate normal versus below normal timed up and go test performance by comparing test performance of community-dwelling and institutionalised elderly women. SETTING AND PARTICIPANTS: 413 community-dwelling and 78 institutionalised mobile elderly women (age range 65-85 years) were enrolled in a cross-sectional study. MEASUREMENTS: timed up and go test duration, residential and mobility status, age, height, weight and body mass index were documented. RESULTS: 92% of community-dwelling elderly women performed the timed up and go test in less than 12 seconds and all community-dwelling women had times below 20 seconds. In contrast only 9% of institutionalised elderly women performed the timed up and go test in less than 12 seconds, 42% were below 20 seconds, 32% had results between 20 and 30 seconds and 26% were above 30 seconds. The 10(th)-90(th) percentiles for timed up and go test performance were 6.0-11.2 seconds for community-dwelling and 12.7-50.1 seconds for institutionalised elderly women. When stratifying participants according to mobility status, the timed up and go test duration increased significantly with decreasing mobility (Kruskall-Wallis-test: p<0.0001). Linear regression modelling identified residential status (p<0.0001) and physical mobility status (p<0.0001) as significant predictors of timed up and go performance. This model predicted 54% of total variation of timed up and go test performance. CONCLUSION: residential and mobility status were identified as the strongest predictors of timed up and go test performance. We recommend the timed up and go test as a screening tool to determine whether an in-depth mobility assessment and early intervention, such as prescription of a walking aid, home visit or physiotherapy, is necessary. Community-dwelling elderly women between 65 and 85 years of age should be able to perform the timed up and go test in 12 seconds or less.

Effects of vitamin D and calcium supplementation on falls: a randomized controlled trial.

Specific receptors for vitamin D have been identified in human muscle tissue. Cross-sectional studies show that elderly persons with higher vitamin D serum levels have increased muscle strength and a lower number of falls. We hypothesized that vitamin D and calcium supplementation would improve musculoskeletal function and decrease falls. In a double-blind randomized controlled trial, we studied 122 elderly women (mean age, 85.3 years; range, 63-99 years) in long-stay geriatric care. Participants received 1200 mg calcium plus 800 IU cholecalciferol (Cal+D-group; n = 62) or 1200 mg calcium (Cal-group; n = 60) per day over a 12-week treatment period. The number of falls per person (0, 1, 2-5, 6-7, >7 falls) was compared between the treatment groups. In an intention to treat analysis, a Poisson regression model was used to compare falls after controlling for age, number of falls in a 6-week pretreatment period, and baseline 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D serum concentrations. Among fallers in the treatment period, crude excessive fall rate (treatment - pretreatment falls) was compared between treatment groups. Change in musculoskeletal function (summed score of knee flexor and extensor strength, grip strength, and the timed up&go test) was measured as a secondary outcome. Among subjects in the Cal+D-group, there were significant increases in median serum 25-hydroxyvitamin D (+71%) and 1,25-dihydroxyvitamin D (+8%). Before treatment, mean observed number of falls per person per week was 0.059 in the Cal+D-group and 0.056 in the Cal-group. In the 12-week treatment period, mean number of falls per person per week was 0.034 in the Cal+D-group and 0.076 in the Cal-group. After adjustment, Cal+D-treatment accounted for a 49% reduction of falls (95% CI, 14-71%; p < 0.01) based on the fall categories stated above. Among fallers of the treatment period, the crude average number of excessive falls was significantly higher in the Cal-group (p = 0.045). Musculoskeletal function improved significantly in the Cal+D-group (p = 0.0094). A single intervention with vitamin D plus calcium over a 3-month period reduced the risk of falling by 49% compared with calcium alone. Over this short-term intervention, recurrent fallers seem to benefit most by the treatment. The impact of vitamin D on falls might be explained by the observed improvement in musculoskeletal function.

Real-time quantitative RT-PCR analysis of human bone marrow stromal cells during osteogenic differentiation in vitro.

We developed and used real-time RT-PCR assays to investigate how the expression of typical osteoblast-related genes by human bone marrow stromal cells (BMSC) is regulated by (i) the culture time in medium inducing osteogenic differentiation and (ii) the previous expansion in medium enhancing cell osteogenic commitment. BMSC from six healthy donors were expanded in medium without (CTR) or with fibroblast growth factor-2 and dexamethasone (FGF/Dex; these factors are known to increase BMSC osteogenic commitment) and further cultivated for up to 20 days with ascorbic acid, beta-glycerophosphate and dexamethasone (these factors are typically used to induce BMSC osteogenic differentiation). Despite a high variability in the gene expression levels among different individuals, we identified the following statistically significant patterns. The mRNA levels of bone morphogenetic protein-2 (BMP-2), bone sialo protein-II (BSP), osteopontin (OP) and to a lower extent cbfa-1 increased with culture time in osteogenic medium (OM), both in CTR- and FGF/Dex-expanded BMSC, unlike levels of alkaline phosphatase, collagen type I, osteocalcin, and osteonectin. After 20 days culture in OM, BMP-2, BSP, and OP were more expressed in FGF/Dex than in CTR-expanded BMSC (mRNA levels were, respectively, 9.5-, 14.9-, and 5.8-fold higher), unlike all the other investigated genes. Analysis of single-colony-derived strains of BMSC further revealed that after 20 days culture in OM, only a subset of FGF/Dex-expanded clones expressed higher mRNA levels of BMP-2, BSP, and OP than CTR-expanded clones. In conclusion, we provide evidence that mRNA levels of BMP-2, BSP, and OP, quantified using real-time RT-PCR, can be used as markers to monitor the extent of BMSC osteogenic differentiation in vitro; using those markers, we further demonstrated that only a few subpopulations of BMSC display enhanced osteogenic differentiation following FGF/Dex expansion.