Nicola Peel

Risk of vertebral fracture and relationship to bone mineral density in steroid treated rheumatoid arthritis.

OBJECTIVES--To determine the prevalence of vertebral fracture in postmenopausal women with steroid treated rheumatoid arthritis (RA), and whether the risk of vertebral fracture could be predicted from measurements of bone mineral density (BMD). METHODS--Vertebral deformities were defined from spine radiographs in 76 postmenopausal women with steroid treated RA (aged 50-79 years) and 347 age matched women from a population based group, using a morphometric technique. Lumbar spine (LS) BMD was measured by dual energy x ray absorptiometry. RESULTS--The odds ratio for vertebral fracture in the women with RA was 6.2 (95% confidence interval 3.2 to 12.3). The decrease in LS-BMD was less than expected for the observed prevalence of vertebral fracture and, among the women with RA, LS-BMD was not lower in those with vertebral fractures. CONCLUSIONS--We conclude that patients with steroid treated RA may have abnormal bone quality, and that LS-BMD cannot be used to predict the risk of vertebral fracture in these patients.

Excretion of pyridinium crosslinks correlates with disease activity and appendicular bone loss in early rheumatoid arthritis.

OBJECTIVE--To establish if urinary excretion rates of the collagen crosslinks pyridinoline and deoxypyridinoline, which are known to be elevated in established rheumatoid arthritis (RA), are useful markers of bone loss in this disease. METHODS--Eight hour urine collections on all patients and 52 controls were performed, and the rates of pyridinoline and deoxypyridinoline excretion were measured. Bone mineral density (BMD), by dual energy x-ray absorption, and full laboratory and clinical assessments were performed. RESULTS--The rates of excretion of pyridinoline and deoxypyridinoline were significantly increased in patients compared with controls (p < 0.001). Pyridinoline excretion was associated with increased disease activity (ESR/CRP) but not disability (HAQ score/Functional Grade), and correlated with BMD loss at the femoral neck (p < 0.01). CONCLUSION--The excretion of collagen crosslinks may be useful as markers of bone and cartilage turnover in patients with RA.

Measuring bone mineral density of the pelvis and proximal femur after total hip arthroplasty

We aimed to evaluate the precision and longitudinal sensitivity of measurement of bone mineral density (BMD) in the pelvis and to determine the effect of bone cement on the measurement of BMD in femoral regions of interest (ROI) after total hip arthroplasty (THA). A series of 29 patients had duplicate dual-energy x-ray absorptiometry (DXA) scans of the hip within 13 months of THA. Pelvic analyses using 3- and 4-ROI models gave a coefficient of variation (CV) of 2.5% to 3.6% and of 2.5% to 4.8%, respectively. Repeat scans in 17 subjects one year later showed a significant change in BMD in three regions using the 4-ROI model, compared with change in only one region with the 3-ROI model (p < 0.05). Manual exclusion of cement from femoral ROIs increased the net CV from 1.6% to 3.6% (p = 0.001), and decreased the measured BMD by 20% (t = 12.1, p < 0.001). Studies of two cement phantoms in vitro showed a small downward drift in bone cement BMD giving a measurement error of less than 0.03 g/cm2/year associated with inclusion of cement in femoral ROIs. Changes in pelvic periprosthetic BMD are best detected using a 4-ROI model. Analysis of femoral ROI is more precise without exclusion of cement although an awareness of its effect on the measurement of the BMD is needed.

Bone mineral density and bone turnover in spinal osteoarthrosis.

OBJECTIVES--To determine whether there was a generalised increase in bone mineral density (BMD) in spinal osteoarthrosis (OA), and to determine the mechanism of this possible protection against osteoporosis as assessed by biochemical markers of bone turnover. METHODS--We studied 375 women (ages 50 to 85) from a population based group. Spinal OA was defined from radiographs as the presence of degenerative changes affecting intervertebral or facet joints. BMD of the lumbar spine (LS), femoral neck (FN) and total body (TB) was measured by dual energy x ray absorptiometry (Lunar DPX). Bone turnover rates were estimated from measurement of biochemical markers of bone formation and resorption (urine deoxypyridinoline (Dpyr) and serum bone specific alkaline phosphatase (BAP)). RESULTS--BMD at each site was greater in the women with spinal OA (mean increase in LS-BMD 7.9%, 95% confidence interval (CI) 1.0 to 15.1; TB-BMD 8.4%, 95% CI 1.9 to 9.7; FN-BMD 6.4%, 95% CI 0.3 to 12.6). Twenty four hour urinary excretion of Dpyr, corrected for TB bone mineral content, and serum BAP were 19% lower in the women with spinal OA (95% CI for Dpyr 4.3 to 31.9%; for BAP 6.3 to 32.0%). CONCLUSIONS--Spinal OA is associated with a generalised increase in BMD and a decreased rate of bone turnover. This suggests that the protective effect of spinal OA against osteoporosis may be mediated by decreased bone turnover.

Risk Factors for Vertebral and Nonvertebral Fracture Over 10 Years: A Population‐Based Study in Women

Risk factors may vary for different types of fracture, in particular for vertebral fractures. We followed 367 women >50 yr of age from a population‐based cohort for up to 10 yr. Factors that predicted vertebral rather than nonvertebral fractures related to physical weakness, poor health, and weight loss. Similar factors were also associated with greater bone loss at the hip.

Use of DXA-Based Structural Engineering Models of the Proximal Femur to Discriminate Hip Fracture

Several DXA‐based structural engineering models (SEMs) of the proximal femur have been developed to estimate stress caused by sideway falls. Their usefulness in discriminating hip fracture has not yet been established and we therefore evaluated these models. The hip DXA scans of 51 postmenopausal women with hip fracture (30 femoral neck, 17 trochanteric, and 4 unspecified) and 153 age‐, height‐, and weight‐matched controls were reanalyzed using a special version of Hologics software that produced a pixel‐by‐pixel BMD map. For each map, a curved‐beam, a curved composite‐beam, and a finite element model were generated to calculate stress within the bone when falling sideways. An index of fracture risk (IFR) was defined over the femoral neck, trochanter, and total hip as the stress divided by the yield stress at each pixel and averaged over the regions of interest. Hip structure analysis (HSA) was also performed using Hologic APEX analysis software. Hip BMD and almost all parameters derived from HSA and SEM were discriminators of hip fracture on their own because their ORs were significantly >1. Because of the high correlation of total hip BMD to HSA and SEM‐derived parameters, only the bone width discriminated hip fracture independently from total hip BMD. Judged by the area under the receiver operating characteristics curve, the trochanteric IFR derived from the finite element model was significant better than total hip BMD alone and similar to the total hip BMD plus bone width in discriminating all hip fracture and femoral neck fracture. No index was better than total hip BMD for discriminating trochanteric fractures. In conclusion, the finite element model has the potential to replace hip BMD in discriminating hip fractures.

Effects of Depot medroxyprogesterone acetate on bone density and bone metabolism before and after peak bone mass: a case-control study.

INTRODUCTION Depot medroxyprogesterone acetate (DMPA; Depo-Provera, Tadworth, UK) contraception is used by more than 9 million women worldwide and has a high usage among teenagers in the United Kingdom and the United States. Previous studies have found that DMPA use is associated with a bone density deficit. OBJECTIVES This case-control matched study aims to eliminate potential confounding factors, identify whether the effect of DMPA on the skeleton is age specific, and determine the effects of DMPA on hormones and bone turnover. DESIGN/PARTICIPANTS We measured bone density, bone turnover, and hormones in individually matched case-control pairs of women: 50 pairs aged 18-25 yr and 50 pairs aged 35-45 yr. RESULTS DMPA use was associated with a 5% bone density deficit at the lumbar spine and hip in women who started DMPA use before age 20 yr but not after age 34 yr. Bone turnover was increased in DMPA users in both age groups. DMPA users had lower estradiol and higher IGF-I than controls, and younger DMPA users had higher dehydroepiandrosterone sulfate than controls. In a multiple regression model, estradiol and IGF-I were associated with bone turnover, but addition of DMPA to the model made the association with estradiol nonsignificant. CONCLUSIONS DMPA use is associated with a bone density deficit at the spine and hip when used before peak bone mass. DMPA acts on the skeleton mainly through estrogen deficiency.

Comparison of Densitometric and Radiographic Vertebral Fracture Assessment Using the Algorithm‐Based Qualitative (ABQ) Method in Postmenopausal Women at Low and High Risk of Fracture

Using ABQ diagnosis, the sensitivity to detect VF of densitometric versus radiographic assessment in 755 postmenopausal women was 71‐81% and specificity was 97%. Misdiagnosis was influenced by image quality and was more common for mild deformities.

Distal forearm fracture as risk factor for vertebral osteoporosis

*

Measurement of bone mass and turnover

Bone mass is the most important determinant of fracture risk. Current bone mass of an individual will be determined by the peak bone mass achieved in early adult life and the subsequent duration and rate of bone loss. In attempting to predict an individuals future risk of fracture it is therefore logical to attempt to assess both of these parameters. Serial measurements of bone mineral density and estimation of the rate of bone turnover may also be used to determine the response to treatment. In this chapter we review the currently available methods of measuring BMD and bone turnover, and discuss their place in the diagnosis and management of osteoporosis.