Clinical Prediction of High-Turnover Bone Disease After Kidney Transplantation.

Bone histomorphometric analysis is the most accurate method for the evaluation of bone turnover, but non-invasive tools are also required. We studied whether bone biomarkers can predict high bone turnover determined by bone histomorphometry after kidney transplantation. We retrospectively evaluated the results of bone biopsy specimens obtained from kidney transplant recipients due to the clinical suspicion of high bone turnover between 2000 and 2015. Bone biomarkers were acquired concurrently. Of 813 kidney transplant recipients, 154 (19%) biopsies were taken at a median of 28 (interquartile range, 18-70) months after engraftment. Of 114 patients included in the statistical analysis, 80 (70%) presented with high bone turnover. Normal or low bone turnover was detected in 34 patients (30%). For discriminating high bone turnover from non-high, alkaline phosphatase, parathyroid hormone, and ionized calcium had the areas under the receiver operating characteristic curve (AUCs) of 0.704, 0.661, and 0.619, respectively. The combination of these markers performed better with an AUC of 0.775. The positive predictive value for high turnover at a predicted probability cutoff of 90% was 95% while the negative predictive value was 35%. This study concurs with previous observations that hyperparathyroidism with or without hypercalcemia does not necessarily imply high bone turnover in kidney transplant recipients. The prediction of high bone turnover can be improved by considering alkaline phosphatase levels, as presented in the logistic regression model. If bone biopsy is not readily available, this model may serve as clinically available tool in recognizing high turnover after engraftment.

Cycling injuries and alcohol.

BACKGROUND: Most of the cycling accidents that occur in Finland do not end up in the official traffic accident statistics. Thus, there is minimal information on these accidents and their consequences, particularly in cases in which alcohol was involved. The focus of the present study is on cycling accidents and injuries involving alcohol in particular. METHODS: Data on patients visiting the emergency department at North Kymi Hospital because of a cycling accident was prospectively collected for two years, from June 1, 2004 to May 31, 2006. Blood alcohol concentration (BAC) was measured on admission with a breath analyser. The severity of the cycling injuries was classified according to the Abbreviated Injury Scale (AIS). RESULTS: A total of 217 cycling accidents occurred. One third of the injured cyclists were involved with alcohol at the time of visiting the hospital. Of these, 85% were males. A blood alcohol concentration of ≥ 1.2 g/L was measured in nearly 90% of all alcohol-related cases. A positive BAC result was more common among males than females (p < 0.001), and head injuries were more common among cyclists where alcohol was involved (AI) (60%) than among sober cyclists (29%) (p < 0.001). Two thirds (64%) of the cyclists with AI were not wearing a bicycle helmet. The figure for serious injuries (MAIS ≥ 3) was similar in both groups. Intoxication with an alcohol level of more than 1.5 g/L and the age of 15 to 24 years were found to be risk factors for head injuries. The mean cost of treatment was higher among sober cyclists than among cyclists with AI (€2143 vs. €1629), whereas in respect of the cost of work absence, the situation was the opposite (€1348 vs. €1770, respectively). CONCLUSIONS: Cyclists involved with alcohol were, in most cases, heavily intoxicated and were not wearing a bicycle helmet. Head injuries were more common among these cyclists than among sober cyclists. As cycling continues to increase, it is important to monitor cycling accidents, improve the accident statistics and heighten awareness of the risks of head injuries when cycling under the influence of alcohol.

Effects of antidepressants on postmenopausal bone loss - A 5-year longitudinal study from the OSTPRE cohort.

BACKGROUND: Osteoporosis and depression are major health problems worldwide. The association between antidepressants, a treatment for depression, and bone health needs more detailed exploration. OBJECTIVE: The present study investigates antidepressant medication use and postmenopausal bone loss over time. METHODS: A total of 1988 women (aged 57-67) participating in the Kuopio Osteoporosis Risk Factor and Prevention Study (OSTPRE) cohort responded to a postal enquiry and had their femoral neck bone mineral density (BMD) measured in 1999 and again in 2004. Data on antidepressant use was obtained from the National Prescription Register. Multiple regression techniques were used to test the associations, before and after adjustment for anthropometric, medical, physical and lifestyle factors. RESULTS: Over the five years of follow-up, 319 (16.0%) women purchased antidepressants. Mean baseline femoral neck BMD for the entire study group was 881mg/cm(2) (SD 123) and mean 5-year bone loss was 6.0mg/cm(2) (SD 4.7). After adjustments, users of tricyclic antidepressants (TCA) had greater annual BMD loss than non-users (-3.6mg/cm(2) vs. -1.1mg/cm(2); P=0.031). Accelerated bone loss was also associated with selective serotonin reuptake inhibitor's (SSRI) use (P=0.001) and use of other antidepressants in a dose-response way, with the latter only among women of low-weight and normal-weight women who had lost weight over the study period. CONCLUSIONS: In conclusion, the use of SSRIs seems to accelerate postmenopausal bone loss in a dose-response manner. Associations between TCA and other antidepressant use and bone loss may also exist. Thus, the possibility of increased risk of osteoporosis should be considered when prescribing antidepressants for postmenopausal women.

Inhaled corticosteroids and bone mineral density at school age: a follow-up study after early childhood wheezing.

OBJECTIVE: The aim of the study was to evaluate the association between previous use of ICS and bone mineral density (BMD) at school age in a cohort followed after early childhood wheezing. METHODS: As part of a prospective follow-up study after hospitalization for wheezing at <24 months of age, BMD was measured in 89 children at 12.3 (median) years of age. Data on ICS use were collected by interviewing the parents, and this was supplemented with data from patient records. Cumulative doses and the duration of ICS use were calculated. Areal BMD (BMDareal , g/cm(2) ) was measured by dual energy X-ray absorptiometry (DXA), and apparent volumetric BMD (aBMDvol , g/cm(3) ) was calculated, for the lumbar spine and femoral neck. Weight, height and pubertal stage were recorded. FINDINGS: Age, sex, and pubertal stage were significantly associated with BMDareal and aBMDvol of the lumbar spine and BMDareal of the femoral neck. The regular use of ICS for >6 months at age <6 years was associated with a lower BMD of the lumbar spine. A lower BMDareal and aBMDvol of the femoral neck were associated with higher cumulative doses of ICS at age 0-12.3 (median) years. The results were robust to adjustment for age, sex, pubertal stage, height, weight, and use of systemic steroids. CONCLUSION: ICS use during childhood may be related to a decrease in BMD at late school age. It is important to use the lowest possible ICS dose that maintains adequate asthma control.

Life satisfaction and bone mineral density among postmenopausal women: cross-sectional and longitudinal associations.

OBJECTIVE: The purpose of this study was to determine whether and how global life satisfaction is associated with bone mineral density (BMD) and bone loss. METHODS: A total of 2167 women from a cohort of Finnish women born in 1932 to 1941 were included in the cross-sectional and 1147 women in the 10-year longitudinal part of the present study. Participants responded to a postal enquiry and underwent femoral BMD densitometry in 1999 (baseline) and 2009 (follow-up). During the follow-up, their life satisfaction was repeatedly measured using a four-item scale. Self-reported data on health, life-style, and medication were used to adjust the multivariate linear regression models. RESULTS: Mean (standard deviation) femoral BMD decreased over the 10-year follow-up from 880 (125) to 846 (122) mg/cm. In the multivariate model, life satisfaction (p = .028) and its improvement (p = .001) predicted reduced bone loss, whereas hospitalization due to depression predicted increased bone loss (B = -0.523 annual % change, standard error = 0.212, p = .014). These effects were independent of each other. CONCLUSIONS: Easily assessed global life satisfaction should be taken into account when effects of aging and prevention of osteoporosis as well as health promotion in postmenopausal women are considered.

Periprosthetic bone mineral density changes after unicondylar knee arthroplasty.

BACKGROUND: Unicompartmental knee arthroplasty (UKA) has received renewed interest in the last decade. UKA involves minor injury to soft tissues, limited removal of bone and delicate preservation of knee anatomy and geometry. In theory, UKA provides an opportunity to restore post-surgical knee kinematics to near normal. HYPOTHESIS: UKA leaves patellofemoral joint free to meet high mechanical forces with no stress-shielding and therefore might preserve bone mineral density (BMD). PATIENTS AND METHODS: We studied 21 patients with osteoarthritis (OA), who had received medial compartment UKA at Kuopio University Hospital between October 1997 and September 2000. BMD was measured by dual-energy X-ray absorptiometry (DEXA), at baseline (within a week after surgery) and at intervals until 7 years. RESULTS: DEXA results were reproducible. The highest rate of periprosthetic bone loss occurred during the first 3 months after UKA. The average loss in BMD was 4.4% (p = 0.039) in the femoral diaphysis and it ranged from 11.2% (p < 0.001) to 11.9% (p = 0.002) in the distal femoral metaphysis; however, BMD changes in these regions, from 2 years to 7 years, were nonsignificant. At the 1-year follow-up, the BMD of the medial tibial metaphysis had increased by 8.9% (p = 0.02), whereas those in the lateral tibial metaphysial (-2.4%) and diaphysial regions (-2.0%) did not change significantly. INTERPRETATIONS: UKA did not preserve periprosthetic BMD in the distal femoral metaphysis, whereas BMD changes in the tibial metaphysis were minor, consistent with a mechanical balance between the medial and lateral tibial compartments. LEVEL OF EVIDENCE 2B: Prospective case control study.

Extra- and intramedullary implants for the treatment of pertrochanteric fractures -- results from a Finnish National Database Study of 14,915 patients.

We analysed registry-based data on 14,915 patients treated for pertrochanteric fracture obtained from the Finnish Health Care Register during the years 1999-2009. Data on the comorbidities, residential status and deaths of the cohort were extracted from several Finnish registries using patients' unique personal identification numbers. The use of intramedullary implants increased substantially during the study period. One-year mortality was slightly higher in the patients treated with intramedullary implant (26.6% vs. 24.9%; P=0.011). In the first year after the fracture, there were more new operations on hip and thigh in patients treated with an intramedullary implant (11.1% vs. 8.9%; P<0.0001). Similarly, there were more new subtrochanteric and diaphyseal fractures of the femur in patients treated with intramedullary implants (3.2% vs. 1.05%; P<0.0001). Our findings suggest that more expensive intramedullary implants do not lead to better clinical outcomes than extramedullary implants for the treatment of pertrochanteric fractures.

Effect of locally administered zoledronic acid on injury-induced intramembranous bone regeneration and osseointegration of a titanium implant in rats.

BACKGROUND: Intramedullary implantation causes injury-induced stimulation of intramembranous bone regeneration. Intramedullary bone injury along with stress shielding may induce periimplant bone loss and cause early aseptic loosening of an implant. The aim of this study was to determine the effect of locally administered zoledronic acid on periimplant bone and injury-induced stimulation of intramembranous bone regeneration in a rat model. METHODS: A total of 28 male rats had a titanium implant inserted into their right femur. During the operation, the medullary canal was lavaged using 20 muM zoledronic acid (Zometa 4 mg/5 ml) or sodium chloride. Follow-up times were 4 and 12 weeks, with each follow-up group consisting of seven rats. The femurs with the titanium implants in situ were harvested, and three microscope sections were cut from each femur. The sections were photographed and analyzed with the Analysis computer program. RESULTS: Between 4 and 12 weeks, the length of fluorescence bone contact increased significantly in both groups (control 15.7% SD and zoledronic acid 18.8% SD), although the difference between the groups was not significant. Periimplant bone volume (thickness) was increased in the 4-week zoledronic acid group compared to the controls (+/-13.4%, P = 0.002) but at 12 weeks the groups no longer differed from each other. CONCLUSIONS: Our results suggest that zoledronic acid may prevent injury-induced bone loss near an intramedullary implant by inhibiting bone resorption shortly after implantation. This may provide better periimplant bone stock during the early postoperative period.

Associations of genetic lactase non-persistence and sex with bone loss in young adulthood.

Some studies have reported that after attainment of peak bone mass (PBM), slow bone loss may occur in both men and women; however, findings are inconsistent. Genetic factors play a significant role in bone loss, but the available evidence is conflicting. Genetic lactase non-persistence (lactase C/C(-13910) genotype) is suggested to increase risk for inadequate calcium intake predisposing to poorer bone health. We investigated whether this genotype is associated with PBM and bone loss in young Finnish adults. Subjects belong to the Cardiovascular Risk in Young Finns Study that is an ongoing multi-centre follow-up of atherosclerosis risk factors. From the original cohort, randomly selected subjects aged 20-29 participated in baseline bone mineral density (BMD) measurements (n=358), and in follow-up measurements 12 years later (n=157). Bone mineral content (BMC) and BMD at lumbar spine (LS) and femoral neck (FN) were measured at baseline and follow-up with dual energy X-ray absorptiometry (DXA). Lactase C/T(-13910) polymorphism was determined by PCR and allele-specific fluorogenic probes. Information on lifestyle was elicited with questionnaires. During the follow-up, bone loss at both bone sites was greater in males (LS BMD: -1.1%, FN BMD: -5.2%) than in females (LS BMD: +2.1%, FN BMD: -0.7%) (both bone sites p=0.001). Younger age predicted greater loss of FN BMC and BMD in females (p=0.013 and p=0.001, respectively). Increased calcium intake predicted FN BMD gain in both sexes (in females B=0.007 g/cm(2)/mg, p=0.002; in males B=0.006, p=0.045), and increased physical activity LS BMD gain in females (B=0.091 g/cm(2)/physical activity point, p=0.023). PBM did not differ between the lactase genotypes, but males with the CC(-13910) genotype seemed to be prone to greater bone loss during the follow-up (LS BMD: C/C vs. T/T p=0.081). In conclusion, bone loss in young adulthood was more common in males than in females and seemed to occur mainly at the femoral neck. Young males with the lactase CC(-13910) genotype may be more susceptible to bone loss; however, calcium intake predicts changes in bone mass more than the lactase genotype.

Bone mineral density in the proximal femur and contralateral knee after total knee arthroplasty.

Osteoarthrosis (OA) is often associated with pain and disability, which are relieved after total knee arthroplasty (TKA), but the nature of bone changes associated with OA is controversial. We examined preoperative hip and contralateral knee bone mineral density (BMD) in patients requiring TKA and monitored the BMD changes postoperatively. Sixty-nine patients, scheduled to have TKA for osteoarthrotic knees, had both hips and contralateral knee BMD measured by dual-energy X-ray absorptiometry (DXA) at the time of operation (baseline) and at 1 yr after operation. X-rays of the knee joints were also taken to evaluate the severity of OA. Preoperatively, 27% and 38% of the patients had total hip BMD Z-score more than 1 SD in the operated side and contralateral hips, respectively. In all regions of interest (ROI), the mean baseline BMD of the affected side proximal femur was significantly lower than that of the contralateral side (p < 0.0005-0.019). The severity of OA was not associated with BMD. During 1-yr follow-up, the postoperative knee status and the physical activity of the patients (AKS score) improved. However, neither the hip nor the nonoperated knee BMDs increased. Knee OA is associated with significantly lower BMD values in the affected side compared with the contralateral hip, and these levels remained similar or decreased during a 1-yr follow-up. We conclude that improved mobility after TKA does not improve the effects of preoperative disuse-associated bone loss in the short term.

Periprosthetic tibial bone mineral density changes after total knee arthroplasty: one-year follow-up study of 69 patients.

BACKGROUND: The critical structure supporting the prosthetic components in total knee arthroplasty (TKA) is tibial trabecular bone. The quality of tibial bone can be evaluated by bone mineral density (BMD) measurements. PATIENTS AND METHODS: We prospectively measured changes in BMD in the proximal tibia after cemented TKA in osteoarthrotic knees. 69 patients were scanned by dual-energy X-ray absorptiometry (DXA) within a week after surgery, and after 3, 6 and 12 months. RESULTS: At baseline, the medial region of interest (ROI) BMD was higher in the varus knees than in the valgus aligned knees (p=0.02). The medial metaphyseal ROI showed a decrease in BMD during the follow-up in preoperatively varus knee joints (p<0.001). In preoperatively valgus knees, there was a slight increase in medial compartment BMD which was not significant (p=0.2). Alignment correction in both groups showed bone remodeling giving similar medial and lateral BMD values, suggesting that the bone became equally strong in both compartments of the metaphysis. There was no association between increasing American Knee Society (AKS) scores and bone remodeling. INTERPRETATION: We suggest that this remodeling is caused by postoperative changes in tibial loading. Our results support the clinical importance of recreating proper valgus alignment of the knee joint in the TKA operation, thus possibly providing better conditions for longevity of the tibial component.

Periprosthetic femoral bone loss after total knee arthroplasty: 1-year follow-up study of 69 patients.

The clinical survival of joint arthroplasties is related to the quality of the surrounding bone environment. Bone mineral density (BMD) is an important measure of bone strength and quality. The aim of this prospective study was to measure the quantitative changes in BMD in the distal femur after cemented total knee arthroplasty (TKA) in osteoarthrotic knee joints. Sixty-nine patients with TKA were scanned postoperatively using dual-energy X-ray absorptiometry (DXA) within a week of surgery, and at 3-, 6-, and 12-month follow-ups. An average decrease in bone density of 17.1% (mean range of 12.1-22.8%) was measured adjacent to the prosthesis at the 12-month follow-up (repeated measures ANOVA P<0.0005). Bone loss was most rapid during the first 3 months after TKA. The clinical status and function parameters of the knee joint, evaluated by the American Knee Society (AKS) score, had improved significantly on the preoperative values at the three- and 12-month follow-ups (P<0.0005). However, improvement in the AKS score was not associated with periprosthetic BMD change (P=0.204), whereas age (P=0.067) and body mass index (P=0.019) correlated with BMD loss for the total metaphyseal region of interest (ROI), by repeated measures ANOVA. We suggest that the observed periprosthetic bone loss was mainly the result of prosthesis-related stress-shielding.

Periprosthetic bone loss after cemented total hip arthroplasty: a prospective 5-year dual energy radiographic absorptiometry study of 15 patients.

In this prospective 5-year study, we determined the periprosthetic bone loss after cemented total hip arthroplasty (THA) in 15 patients using dual energy X-ray absorptiometry (DXA). A reduction in the periprosthetic bone mineral density (BMD) of 5-18% occurred in all Gruen regions, or regions of interest (ROI), during the first 3 months after THA. The bone loss continued up to 6 months in almost all ROIs. From 1 to 5 years, we found only minor changes in BMD in periprosthetic bone. After the follow-up, the mean greatest bone loss (26%) was seen in the femoral calcar area. The reduction in mean BMD was 5% in men, and 16% in women. The lower the preoperative BMD, the higher was the postoperative bone loss. We found that after the phase of acute bone loss, further loss was minimal, reflecting merely the normal ageing of bone after uncomplicated THA.