Distal fusion level, complications, and reoperations in individuals with cerebral palsy undergoing surgery for scoliosis.

PURPOSE: To compare radiological outcome, complications and reoperations in individuals with cerebral palsy and scoliosis fused to the fifth lumbar vertebra (L5), the sacrum, or the ilia. METHODS: 208 individuals were identified in the national quality registry Swespine. Lowest level of fusion was L5 in 58, the sacrum in 92, and the ilia in 58 individuals. A subanalysis on 58 matched pairs operated to L5 or the pelvis (sacrum = 42, ilia = 16) with similar pelvic obliquity (± 5°) was performed. RESULTS: The median (interquartile range) follow-up for the last radiograph was 1.7 (1.7) years and for reoperations 6.0 (5.9) years. Preoperatively, median Cobb angle of the major curve was 65° (23°) in the L5 group, 68° (28°) in the sacrum group, and 78° (25°) in the ilia group (p = 0.006). Preoperative median pelvic obliquity according to Maloney was 16° (19°), 21° (13°), and 27° (28°), respectively (p = 0.004). Immediate postoperative Cobb angles were 28° (18°), 28° (16°), and 32° (25°), respectively (p = 0.11). Immediate postoperative pelvic obliquity was 7° (10°), 7° (8°), and 8° (10°), respectively (p = 0.28). The median change in pelvic obliquity from the first to the last postoperative radiograph was - 5° (7°), - 3° (6°), - 3° (6°), respectively (p = 0.55). 7 (12%), 11 (12%), and 7 (12%) patients required at least one reoperation (p = 1.0), respectively. In the matched analysis, no significant differences in the radiological outcomes were found (all p ≥ 0.38). CONCLUSIONS: Maintained curve and pelvic obliquity correction with no significant difference in complication and reoperation rates were found irrespective of distal fusion level.

Minor effect of loss to follow-up on outcome interpretation in the Swedish spine register.

BACKGROUND AND PURPOSE: Loss to follow-up in observational studies may skew results and hamper study reliability. We evaluated the importance of loss to follow-up in the Swedish spine register. PATIENTS: Patients operated in the lumbar spine and scheduled for a postal questionnaire follow-up during part of 2016 were identified. Out of the 351 patients, 203 had responded. After multiple attempts, 115 of the 148 non-responders were reached; 68 returned the complete questionnaire; and 47 answered a brief questionnaire by phone. Analyses were made with the Chi-square test, analysis of covariance or logistic regression. Some analyses were adjusted. RESULTS: At baseline, the non-responders were younger than the responders (55 vs 61 years, p < 0.001) and had higher Oswestry Disability Index (ODI) (54 vs 48, p = 0.003), lower SF-36 physical component summary score (PCS) (36 vs 40, p = 0.011) and lower EQ-5D (0.17 vs 0.27, p = 0.018). Mean back pain, leg pain, ODI, EQ-5D, SF-36 mental component summary score (MCS) improved significantly in both groups (all p < 0.001). SF-36 PCS did not improve in the non-responder group (p = 0.063). Non-responders perceived less improvement in back pain (global assessment back 60% vs 72%, p = 0.002). At follow-up, there were no differences in patient-reported outcome measures between the groups (all p ≥ 0.06), with the exception of a lower SF-36 MCS among the non-responders (p = 0.015). INTERPRETATION: After surgery for lumbar spine degenerative disorders, non-responders achieve similar outcome as responders in the Swedish spine register, with the exception of a lower mental health and less perceived improvement in back pain. These slides can be retrieved under Electronic Supplementary Material.

Long-term outcome after spinal fusion for isthmic spondylolisthesis in adults.

BACKGROUND CONTEXT: Data on the long-term outcome after fusion for isthmic spondylolisthesis are scarce. PURPOSE: To study patient-reported outcomes and adjacent segment degeneration (ASD) after fusion for isthmic spondylolisthesis and to compare patient-reported outcomes with a control group. STUDY DESIGN/SETTING: A prospective study including a cross-sectional control group. PATIENT SAMPLE: Patients with isthmic spondylolisthesis underwent posterior lumbar interbody fusion (PLIF) (n=86) or posterolateral fusion (PLF) (n=77). Patient-reported outcome data were available for 73 patients in the PLIF group and 71 in the PLF group at a mean of 11 (range 5-16) years after baseline. Seventy-seven patients in the PLIF group and 54 in the PLF group had radiographs at a mean of 14 (range 9-19) years after baseline. One hundred thirty-six randomly selected persons from the population served as controls for the patient-reported outcomes. OUTCOME MEASURES: Patient-reported outcomes include the following: global outcome, Oswestry Disability Index, Disability Rating Index, and Short Form 36. The ASD was determined from radiographs using the University of California Los Angeles (UCLA) grading scale. METHODS: The chi-square test or analysis of covariance (ANCOVA) was used for group comparisons. The ANCOVA was adjusted for follow-up time, smoking, Meyerding slippage grade, teetotaler (yes/no) and, if available, the baseline level of the dependent variable. RESULTS: There were no significant patient-reported outcome differences between the PLIF group and the PLF group. The prevalence of ASD was 42% (32/77) in the PLIF group and 26% (14/54) in the PLF group (p=.98). The patient-reported outcome data indicated lower physical function and more pain in individuals with surgically treated isthmic spondylolisthesis compared to the controls. CONCLUSIONS: PLIF and PLF groups had similar long-term patient-reported and radiological outcomes. Individuals with isthmic spondylolisthesis have lower physical function and more pain several years after surgery when compared to the general population.

Implant density is not related to patient-reported outcome in the surgical treatment of patients with idiopathic scoliosis.

Aims: There is little information about the optimum number of implants to be used in the surgical treatment of idiopathic scoliosis. Retrospective analysis of prospectively collected data from the Swedish spine register was undertaken to discover whether more implants per operated vertebra (implant density) leads to a better outcome in the treatment of idiopathic scoliosis. The hypothesis was that implant density is not associated with patient-reported outcomes, the correction of the curve or the rate of reoperation. Patients and Methods: A total of 328 patients with idiopathic scoliosis, aged between ten and 20 years at the time of surgery, were identified in the Swedish spine register (Swespine) and had patient reported outcomes including the Scoliosis Research Society 22r instrument (SRS-22r) score, EuroQol 5 dimensions quality of life, 3 level (EQ-5D-3L) score and a Viual Analogue Score (VAS) for back pain, at a mean follow-up of 3.1 years and reoperation data at a mean follow-up of 5.5 years. Implant data and the correction of the curve were assessed from radiographs, preoperatively and a mean of 1.9 years postoperatively. The patients were divided into tertiles based on implant density. Data were analyzed with analysis of variance, logistic regression or log-rank test. Some analyses were adjusted for gender, age at the time of surgery, the flexibility of the major curve and follow-up. Results: The mean number of implants per operated vertebra in the low, medium and high-density groups were 1.36 (1.00 to 1.54), 1.65 (1.55 to 1.75) and 1.91 (1.77 to 2.00), respectively. There were no statistically significant differences in the correction of the curve, the SRS-22r total score, EQ-5D-3L index or number of reoperations between the groups (all p > 0.34). In the SRS-22r domains, self-image was marginally higher in the medium implant density group (p = 0.029) and satisfaction marginally higher in the high implant density group (p = 0.034). Conclusion: These findings suggest that there is no clear advantage in using a high number of implants per operated vertebra in the surgical treatment of patients with idiopathic scoliosis. Cite this article: Bone Joint J 2018;100-B:1080-6.

Genetics and pathogenesis of idiopathic scoliosis.

Idiopathic scoliosis (IS), the most common spinal deformity, affects otherwise healthy children and adolescents during growth. The aetiology is still unknown, although genetic factors are believed to be important. The present review corroborates the understanding of IS as a complex disease with a polygenic background. Presumably IS can be due to a spectrum of genetic risk variants, ranging from very rare or even private to very common. The most promising candidate genes are highlighted.

Similar result after non-elective and elective surgery for lumbar disc herniation: an observational study based on the SweSpine register.

PURPOSE: Surgery for lumbar disc herniation (LDH) is most often elective, but intense pain may require more urgent, non-elective, treatment. It was hypothesized that non-elective treatment could be associated with a less favourable outcome than elective surgery. The aim of this study was to compare 1-2-year outcome after non-elective and elective surgery for treatment of para-median LDH using data from the Swedish Spine register (SweSpine). METHODS: Pre- and postoperative data were available for 301 non-elective and 2364 elective cases. Patient reported outcome measures (PROMs) were; Visual Analogue Scale (VAS) leg and back pain, Oswestry Disability Index (ODI), EuroQol five-Dimensions (EQ-5D) and patient satisfaction. Postoperative p values were adjusted for baseline differences. RESULTS: Preoperative mean (SD) in the non-elective and elective groups were for VAS leg pain 81 (22) and 65 (24), for VAS back pain 51 (33) and 45 (28), for ODI 66 (20) and 45 (17) and for EQ-5D 0.024 (0.35) and 0.31 (0.33), respectively, (p for all <0.001). Postoperative VAS leg pain was 23 (28) in the non-elective group and 20 (26) in the elective group (p = 0.19). Corresponding figures were for VAS back pain 25 (27) and 24 (27) (p = 0.69), ODI 19 (17) and 17 (17) (p = 0.052) and for EQ-5D 0.70 (0.28) and 0.73 (0.29) (p = 0.73). Patient satisfaction did not differ between the groups (p = 0.78). CONCLUSIONS: Even if non-elective patients preoperatively had substantially more pain, higher disability and poorer quality of life than elective patients, postoperative differences were clinically small. Patient satisfaction did not differ.

Smoking, smoking cessation, and fracture risk in elderly women followed for 10 years.

UNLABELLED: This study examines the impact of smoking and smoking cessation on fracture risk in 75-year-old women followed for 10 years. Smoking increased fracture risk, especially for vertebral fractures. Smoking cessation decreased the risk for vertebral fractures but not for other fracture types. INTRODUCTION: The purpose of this study was to examine effects of smoking and smoking cessation on fracture risk. METHODS: This prospective observational population-based study followed 1033 women during 10 years from age 75. Data regarding smoking were collected at age 75. Hazard ratios (HRs) and 95 % confidence intervals for fracture were calculated using competing risks proportional hazards regression. RESULTS: Both former smokers and current smokers had an increased risk for any fracture (HR 1.30; 1.03-1.66, and HR 1.32; 1.01-1.73, respectively) and any osteoporotic fracture (hip, proximal humerus, distal radius, vertebra) (HR 1.31; 1.01-1.70 and HR 1.49; 1.11-1.98, respectively) compared to non-smokers. Former smokers had an increased risk for proximal humerus fractures (HR 2.23; 1.35-3.70), and current smokers had an increased risk for vertebral fractures (HR 2.30; 1.57-3.38) compared to non-smokers. After adjustment for weight, previous fractures, alcohol habits, bone mineral density (BMD), use of corticoids, vitamin D, bisphosphonates, and previous falls, former smokers had an increased risk for proximal humerus fracture (HR 2.07; 1.19-3.57) and current smokers had an increased risk for osteoporotic (HR 1.47; 1.05-2.05) and vertebral fractures (HR 2.50; 1.58-3.95) compared to non-smokers. Former smokers had a decreased risk for vertebral fractures, but not for other types of fractures, compared to current smokers. CONCLUSIONS: Smoking increased the risk for fracture among elderly women, especially vertebral fractures. Smoking cessation decreased the risk for vertebral fractures but not for other types of fractures.

Markers of inflammation and fibrinolysis in relation to outcome after surgery for lumbar disc herniation. A prospective study on 177 patients.

PURPOSE: The role of inflammation and fibrinolysis for the development of back pain and sciatica has been discussed. The aim of this study was to assess the relationship between markers of inflammation and fibrinolysis, to predict the outcome after surgery for lumbar disc herniation. METHODS: 177 patients were recruited. High sensitive C-reactive protein (hsCRP), plasminogen activator inhibitor 1 (PAI-1), fibrinogen, and D-dimer were analyzed preoperatively. Visual analogue scale (VAS) for back and leg pain, Oswestry Disability Index (ODI), and EuroQol 5 Dimensions (EQ-5D) were assessed preoperatively and at 6 weeks, 6-, 12-, and 24- months postoperatively. Dichotomization was made at the median for the laboratory analyses, and between the worst quartile and the other three quartiles for the outcome variables. Logistic regression was used to determine the odds ratios (OR) and 95 % confidence intervals (CI). RESULTS: The associations between PAI-1 and outcome seemed to be most prominent at the 6 and 12-month follow-up. When being in the upper half of PAI-1, the OR for being in the worst quartile of VAS back pain 12 months postoperatively was 3.33 (1.56-7.10). The corresponding OR for VAS leg pain was 2.46 (1.18-5.10), for ODI 2.83 (1.35-5.94) and for EQ-5D 2.73 (1.30-5.75). The OR for hsCRP was 2.10 (1.03-4.29) for being in the worst quartile of VAS back pain. Fibrinogen or D-dimer was not associated with any outcome variable. CONCLUSIONS: High PAI-1, a marker of fibrinolysis, was fairly consistently associated with poor outcome, while hsCRP, fibrinogen, and D-dimer were not.

Outcome of surgical treatment of lumbar disc herniation in young individuals.

Lumbar disc herniation (LDH) is uncommon in youth and few cases are treated surgically. Very few outcome studies exist for LDH surgery in this age group. Our aim was to explore differences in gender in pre-operative level of disability and outcome of surgery for LDH in patients aged ≤ 20 years using prospectively collected data. From the national Swedish SweSpine register we identified 180 patients with one-year and 108 with two-year follow-up data ≤ 20 years of age, who between the years 2000 and 2010 had a primary operation for LDH. Both male and female patients reported pronounced impairment before the operation in all patient reported outcome measures, with female patients experiencing significantly greater back pain, having greater analgesic requirements and reporting significantly inferior scores in EuroQol (EQ-5D-index), EQ-visual analogue scale, most aspects of Short Form-36 and Oswestry Disabilities Index, when compared with male patients. Surgery conferred a statistically significant improvement in all registered parameters, with few gender discrepancies. Quality of life at one year following surgery normalised in both males and females and only eight patients (4.5%) were dissatisfied with the outcome. Virtually all parameters were stable between the one- and two-year follow-up examination. LDH surgery leads to normal health and a favourable outcome in both male and female patients aged 20 years or younger, who failed to recover after non-operative management.

Fracture predictive ability of physical performance tests and history of falls in elderly women: a 10-year prospective study.

UNLABELLED: In a large cohort of elderly women followed for 10 years, we found that balance, gait speed, and self-reported history of fall independently predicted fracture. These clinical risk factors are easily evaluated and therefore advantageous in a clinical setting. They would improve fracture risk assessment and thereby also fracture prevention. INTRODUCTION: The aim of this study was to identify additional risk factors for osteoporosis-related fracture by investigating the fracture predictive ability of physical performance tests and self-reported history of falls. METHODS: In the population-based Osteoporosis Prospective Risk Assessment study (OPRA), 1044 women were recruited at the age of 75 and followed for 10 years. At inclusion, knee extension force, standing balance, gait speed, and bone mineral density (BMD) were examined. Falls the year before investigation was assessed by questionnaire. Cox proportional hazards regression analysis was used to determine fracture hazard ratios (HR) with BMD, history of fracture, BMI, smoking habits, bisphosphonate, vitamin D, glucocorticoid, and alcohol use as covariates. Continuous variables were standardized and HR shown for each standard deviation change. RESULTS: Of all women, 427 (41%) sustained at least one fracture during the 10-year follow-up. Failing the balance test had an HR of 1.98 (1.18-3.32) for hip fracture. Each standard deviation decrease in gait speed was associated with an HR of 1.37 (1.14-1.64) for hip fracture. Previous fall had an HR of 1.30 (1.03-1.65) for any fracture; 1.39 (1.08-1.79) for any osteoporosis-related fracture; and 1.60 (1.03-2.48) for distal forearm fracture. Knee extension force did not show fracture predictability. CONCLUSION: The balance test, gait speed test, and self-reported history of fall all hold independent fracture predictability. Consideration of these clinical risk factors for fracture would improve the fracture risk assessment and subsequently also fracture prevention.

Serum level of cartilage oligomeric matrix protein is lower in children with idiopathic scoliosis than in non-scoliotic controls.

PURPOSE: The etiology of idiopathic scoliosis remains unknown, but growth is a risk factor for progression. Growth pattern differs in children with and without scoliosis. Cartilage oligomeric matrix protein (COMP) may be associated with scoliosis and growth. We, therefore, studied COMP in children with and without idiopathic scoliosis. METHODS: We included 105 children, with mean age 14.4 years (range 10-16), under observation or treatment for idiopathic scoliosis, and 103 children from an age-matched population-based cohort. COMP was measured in serum at the time of inclusion. Growth velocity was estimated from repeated height measurements. T tests, analysis of covariance or linear regression were used for statistical comparisons. RESULTS: COMP was mean (SD) 11 (5) units/liter (U/L) in children with scoliosis and 13 (5) U/L in the control cohort (p = 0.005, adjusted for sex and sampling time of the day). When patients and controls were analyzed together, high COMP was correlated with high growth velocity (ß = 0.19, p = 0.003). When patients and controls were analyzed separately, COMP was correlated with growth velocity in children with scoliosis (ß = 0.27, p = 0.007), but not in children without scoliosis (ß = 0.02, p = 0.83) (all analyses adjusted for age, sex and sampling time). Low COMP was significantly correlated with large curve size in children with scoliosis (ß = -0.29, p = 0.003), but not after adjustment for age, sex and sampling time (ß = -0.16; p = 0.14). CONCLUSION: COMP was lower in children with idiopathic scoliosis than in a control cohort. In children with scoliosis, high COMP was modestly correlated with high growth velocity, but not with curve severity.

Vitamin D insufficiency over 5 years is associated with increased fracture risk-an observational cohort study of elderly women.

UNLABELLED: This study of elderly Swedish women investigated the association between chronic vitamin D insufficiency and osteoporotic fractures occurring between ages 80-90. The incidence and risk of hip and major osteoporotic fractures was significantly higher in elderly women with low vitamin D levels maintained over 5 years. INTRODUCTION: Vitamin D insufficiency among the elderly is common; however, relatively little is known about the effects of long-term hypovitaminosis D on fracture. We investigated sequential assessment of serum 25(OH)D at age 75 and 80 to determine if continuously low 25(OH)D levels are associated with increased 10-year fracture incidence. METHODS: One thousand forty-four Swedish women from the population-based OPRA cohort, all 75 years old, attended at baseline (BL); 715 attended at 5 years. S-25(OH)D was available in 987 and 640, respectively and categorized as: <50 (Low), 50-75 (Intermediate), and >75 nmol/L (High). Incident fracture data was collected with maximum follow-up to 90 years of age. RESULTS: Hip fracture incidence between age 80-85 was higher in women who had low 25(OH)D at both baseline and 5 years (22.2 % (Low) vs. 6.6 % (High); p = 0.003). Between age 80-90, hip fracture incidence was more than double that of women in the high category (27.9 vs. 12.3 %; p = 0.006). Within 5-years, 50 % of women in the continuously low group compared to 34 % in the continuously high 25(OH)D group had an osteoporotic fracture (p = 0.004) while 10-year incidence was higher compared to the intermediate (p = 0.020) but not the high category (p = 0.053). The 10-year relative risk of hip fracture was almost three times higher and osteoporotic fracture risk almost doubled for women in the lowest 25(OH)D category compared to the high category (HR 2.7 and 1.7; p = 0.003 and 0.023, respectively). CONCLUSION: In these elderly women, 25(OH)D insufficiency over 5-years was associated with increased 10-year risk of hip and major osteoporotic fractures.

Vitamin D status and bone health in immigrant versus Swedish women during pregnancy and the post-partum period.

OBJECTIVE: We evaluated the association between vitamin D status and bone health in pregnant and post-partum immigrant versus Swedish women. METHODS: We consecutively recruited 41 immigrant and 19 age-matched healthy native Swedish women. Serum 25-hydroxy vitamin D(3) [25(OH)D] and parathyroid hormone (PTH) were analyzed at pregnancy week 12 and 6-12 months postpartum. Dual X-ray absorptiometry (DXA) of the hip and lumbar spine, and peripheral quantitative computed tomography (pQCT) of the radius and tibia were analyzed 6-12 months postpartum. RESULTS: The mean±SD 25(OH)D in gestational week 12 was 20±11 nmol/L among the immigrants and 60±17 nmol/L among the Swedish women (p<0.001). The postpartum 25(OH)D was 29±18 nmol/L among the immigrants and 53±19 nmol/L among the Swedish women (p=0.003). BMD measured with DXA and pQCT did not differ significantly between groups. The ratio of cortical and trabecular density, a potential sign of osteomalacia, did not differ between groups. There were no significant correlations between 25(OH)D and the bone density measurements. CONCLUSIONS: Immigrant young women in Sweden are at a high risk of persistent and pronounced 25(OH)D deficiency. However, radiological measures of bone health were not affected by persisting low 25(OH)D. The health consequences of 25(OH)D deficiency should be studied in future studies.

Degenerative changes at the lumbar spine--implications for bone mineral density measurement in elderly women.

UNLABELLED: Degenerative changes of the lumbar spine may lead to misinterpretation of bone mineral density (BMD) measurements and cause underdiagnosis of osteoporosis. This longitudinal study of 1,044 women, 75 years at inclusion and followed for 10 years, shows that identification of apparent degenerative changes on the dual energy X-ray absorptiometry (DXA) scan can increase the proportion diagnosed. INTRODUCTION: In the elderly, degenerative manifestations in the lumbar spine may result in falsely elevated BMD values, consequently missing a large proportion of those with osteoporosis. Our aim was to determine the distribution and impact of degenerative changes on lumbar spine DXA over time and its clinical implications. METHODS: Participants were 1,044 women from the population-based Osteoporosis Risk Assessment cohort. All women were 75 years old at invitation and followed up after 5 years (n=715) and 10 years (n=382). Degenerative changes were evaluated visually on the DXA image for each vertebra L1 to L4 (intraobserver precision kappa values of 0.66-0.70). RESULTS: At baseline, apparent degenerative changes were more frequent in the inferior segments of the lumbar spine [5% (L1), 15% (L2), 26% (L3), and 36% (L4)] and increased over time. At 10 years, the prevalences were 20% (L1), 39% (L2), 59% (L3), 72% (L4), resulting in a significant increase in overall BMD. In women without apparent degenerative changes, BMD remained stable between 75 and 85 rather than an expected bone loss. At baseline, 37% had osteoporosis (BMD<-2.5) at L1-L4; exclusion of women with apparent degenerative changes increased this proportion to 47%. Using L1-L2, which was less prone to degenerative changes, 46% of women were classified as osteoporotic regardless of degenerative changes. CONCLUSION: Degenerative changes were very common in elderly women, accelerated disproportionately over time, were increasingly frequent from vertebrae L1 to L4, and had significant impact on diagnosing osteoporosis. This suggests that routine reporting of spine BMD at L1-L2 would add valuable information for reassessment and monitoring.

Variation in the PTH gene, hip fracture, and femoral neck geometry in elderly women.

Parathyroid hormone (PTH) is a principal regulator of calcium homeostasis. Previously, we studied single-nucleotide polymorphisms present in the major genes in the PTH pathway (PTH, PTHrP, PTHR1, PTHR2) in relation to bone mineral density (BMD) and fracture incidence. We found that haplotypes of the PTH gene were associated with fracture risk independent of BMD. In the present study, we evaluated the relationship between PTH haplotypes and femoral neck bone size. Hip structure analysis and BMD of the femoral neck was assessed by DXA in elderly women from the Malmö Osteoporosis Prospective Risk Assessment study. Data on hip fracture, sustained as a result of low trauma, after the age of 45 years were also analyzed. Haplotypes derived from six polymorphisms in the PTH locus were analyzed in 750 women. Carriers of haplotype 9 had lower values for hip geometry parameters cross-sectional moment of inertia (P = 0.029), femoral neck width (P = 0.049), and section modulous (P = 0.06), suggestive of increased fracture risk at the hip. However, this did not translate into an increased incidence of hip fracture in the studied population. Women who suffered a hip fracture compared to those who had not had longer hip axis length (HAL) (P < 0.001). HAL was not significantly different among haplotypes. Polymorphisms in the PTH gene are associated with differences in aspects of femoral neck geometry in elderly women; however, the major predictor of hip fracture in our population was HAL, to which PTH gene variation does not contribute significantly.

Bone turnover markers are correlated with quantitative ultrasound of the calcaneus: 5-year longitudinal data.

SUMMARY: Associations between bone turnover markers and calcaneal ultrasound (quantitative ultrasound, QUS) were studied in a population-based sample of 810 elderly women. Baseline bone turnover markers correlated with baseline QUS as well as with 5-year prospective changes in QUS. INTRODUCTION: Bone turnover markers are associated with areal bone mineral density, but the knowledge on the association with QUS is limited. METHODS: Eight hundred ten women, all 75 years old, were investigated at baseline. Five hundred six completed a 5-year follow-up. Bone turnover markers and calcaneal QUS [speed of sound (SoS), broadband ultrasound attenuation (BUA), stiffness] were investigated at baseline. QUS was investigated at follow-up. RESULTS: All bone turnover markers were correlated with baseline QUS [standardized regression (Beta(std)) values from -0.07, p < 0.05 to -0.23, p < 0.001], with the exception of bone-specific alkaline phosphatase (S-Bone ALP) which was not correlated with BUA and stiffness index. When the correlations between baseline bone turnover markers and 5-year changes in QUS were analyzed, three serum osteocalcins were correlated with changes of SoS and stiffness index (Beta(std) = -0.11, p < 0.05 to -0.17, p < 0.001). Also S-CTX-I correlated with changes of SoS and stiffness index (Beta(std) = -0.10 and -0.09, respectively, p < 0.05). S-TRACP5b, urinary deoxypyridinoline/crea, and U-MidOC/crea correlated with changes of SoS (Beta(std) = -0.10 and p < 0.05 for all). S-Bone ALP did not correlate with change of QUS. None of the bone turnover markers correlated with changes of BUA. CONCLUSIONS: Bone turnover markers correlate with concomitantly assessed QUS as well as with longitudinal change in QUS.

Genetic variation in the PTH pathway and bone phenotypes in elderly women: evaluation of PTH, PTHLH, PTHR1 and PTHR2 genes.

INTRODUCTION: Parathyroid hormone (PTH) is a key regulator of calcium metabolism. Parathyroid hormone-like hormone (PTHrP) contributes to skeletal development through regulation of chondrocyte proliferation and differentiation during early bone growth. Both PTH and PTHrP act through the same receptor (PTHR1). A second receptor, PTHR2, has been identified although its function is comparatively unknown. PTH hyper-secretion induces bone resorption, whereas intermittent injection of PTH increases bone mass. To explore the effects of genetic variation in the PTH pathway, we have analysed variations in PTH, PTHLH, PTHR1 and PTHR2 in relation to bone mass and fracture incidence in elderly women. MATERIALS AND METHODS: This study includes 1044 elderly women, all 75 years old, from the Malmö Osteoporosis Prospective Risk Assessment study (OPRA). Single nucleotide polymorphisms (SNPs) from 4 genes and derived haplotypes in the PTH signaling pathway were analysed in 745-1005 women; 6 SNPs in the PTH gene and 3 SNPs each in the PTHLH, PTHR1 and PTHR2 genes were investigated in relation to BMD (assessed at baseline), fracture (434 prevalent fractures of all types over lifetime, self-reported and 174 incident fractures up to 7 years, X-ray verified) and serum PTH. RESULTS AND CONCLUSION: Individually, SNPs in the 4 loci did not show any significant association with BMD. Neither were PTHLH, PTHR1 and PTHR2 polymorphisms associated with fracture. Three of 5 common haplotypes, accounting for >98% of alleles at the PTH locus, were identified as independent predictors of fracture. Haplotype 9 (19%) was suggestive of an association with fractures of any type sustained during lifetime (p=0.018), with carriers of one or more copies of the haplotype having the lowest incidence (p=0.006). Haplotypes 1 (13%) and 5 (37%) and 9 were suggestive of an association with fractures sustained between 50 and 75 years (p=0.02, p=0.013 and p=0.034). Carriers of haplotypes 1 and 5 were more likely to suffer a fracture (haplotype 1, p=0.045; haplotype 5, p=0.008). We conclude, that while further genotyping across the gene is recommended, in this cohort of elderly Swedish women, polymorphisms in PTH may contribute to the risk of fracture through mechanisms that are independent of BMD.

Rates of fracture in participants and non-participants in the Osteoporosis Prospective Risk Assessment study.

We invited 1604 randomly selected women, all 75 years of age, to participate in a study on the risk factors for fracture. The women were divided into three groups consisting of 1044 (65%) who attended the complete study, 308 (19%) respondents to the study questionnaire only and 252 (16%) who did not respond. The occurrence of the life-time fracture was ascertained from radiological records in all groups and by questionnaires from the attendees and respondents. According to the radiological records, fewer of the questionnaire respondents (88 of 308, 28.6%) and non-respondents (68 of 252, 27%) had sustained at least one fracture when compared with the attendees (435 of 1044, 41.7%; chi-squared test, p < 0.001). According to the questionnaire, fewer of the respondents (96 of 308, 31.1%) had sustained at least one previous fracture when compared with the attendees (457 of 1044, 43.7%; chi-squared test, p < 0.001). Any study concerning the risk of fracture may attract those with experience of a fracture which explains the higher previous life-time incidence among the attendees. This factor may cause bias in epidemiological studies.

Prediction of bone loss using biochemical markers of bone turnover.

UNLABELLED: The association between baseline levels of eleven bone turnover markers and 5-year rate of bone density change was prospectively studied in a population-based sample of 601 75-year-old women. Several bone formation and resorption markers as well as urinary osteocalcin were modestly correlated to rate of bone density change. INTRODUCTION: Prediction of bone loss by bone turnover markers (BTMs) has been investigated with conflicting results. There is limited information in the elderly. METHODS: Eleven bone turnover markers were analyzed in 75-year old women in the OPRA study (n = 601) and compared to the 5-year change of areal bone mineral density (aBMD) in seven skeletal regions. RESULTS: Annual aBMD change varied between +0.4% (spine) and -2.0% (femoral neck). Significant associations (p < 0.01) were found for four different serum osteocalcins (S-OCs) (standardized regression coefficient -0.20 to -0.22), urinary deoxypyridinoline (-0.19), serum TRACP5b (-0.19), serum CTX-I (-0.21), two of the three urinary osteocalcins (U-OCs) (-0.16) and aBMD change of the leg region (derived from the total body measurement). After adjustment for baseline aBMD, associations were found for all S-OCs (-0.11 to -0.16), two of the three U-OCs (-0.14 to -0.16) and aBMD change at the total hip, and for three of the four S-OCs (-0.14 to -0.15), S-TRACP5b (-0.11), two of the three U-OCs (-0.14 to -0.15) and aBMD change at the femoral neck. There were no significant results concerning aBMD change at the spine. CONCLUSION: This study indicates that BTMs are correlated with aBMD loss in some skeletal regions in elderly women.