A systematic review on the performance of fracture risk assessment tools: FRAX, DeFRA, FRA-HS.

PURPOSE: Preventing fragility fractures by treating osteoporosis may reduce disability and mortality worldwide. Algorithms combining clinical risk factors with bone mineral density have been developed to better estimate fracture risk and possible treatment thresholds. This systematic review supported panel members of the Italian Fragility Fracture Guidelines in recommending the use of best-performant tool. The clinical performance of the three most used fracture risk assessment tools (DeFRA, FRAX, and FRA-HS) was assessed in at-risk patients. METHODS: PubMed, Embase, and Cochrane Library were searched till December 2020 for studies investigating risk assessment tools for predicting major osteoporotic or hip fractures in patients with osteoporosis or fragility fractures. Sensitivity (Sn), specificity (Sp), and areas under the curve (AUCs) were evaluated for all tools at different thresholds. Quality assessment was performed using the Quality Assessment of Diagnostic Accuracy Studies-2; certainty of evidence (CoE) was evaluated using the Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS: Forty-three articles were considered (40, 1, and 2 for FRAX, FRA-HS, and DeFRA, respectively), with the CoE ranging from very low to high quality. A reduction of Sn and increase of Sp for major osteoporotic fractures were observed among women and the entire population with cut-off augmentation. No significant differences were found on comparing FRAX to DeFRA in women (AUC 59-88% vs. 74%) and diabetics (AUC 73% vs. 89%). FRAX demonstrated non-significantly better discriminatory power than FRA-HS among men. CONCLUSION: The task force formulated appropriate recommendations on the use of any fracture risk assessment tools in patients with or at risk of fragility fractures, since no statistically significant differences emerged across different prediction tools.

The assessment of vertebral fractures in elderly women with recent hip fractures: the BREAK Study.

UNLABELLED: This study aimed to evaluate the prevalence of vertebral fractures in elderly women with a recent hip fracture. The burden of vertebral fractures expressed by the Spinal Deformity Index (SDI) is more strictly associated with the trochanteric than the cervical localization of hip fracture and may influence short-term functional outcomes. INTRODUCTION: This study aimed to determine the prevalence and severity of vertebral fractures in elderly women with recent hip fracture and to assess whether the burden of vertebral fractures may be differently associated with trochanteric hip fractures with respect to cervical hip fractures. METHODS: We studied 689 Italian women aged 60 years or over with a recent low trauma hip fracture and for whom an adequate X-ray evaluation of spine was available. All radiographs were examined centrally for the presence of any vertebral deformities and radiological morphometry was performed. The SDI, which integrates both the number and the severity of fractures, was also calculated. RESULTS: Prevalent vertebral fractures were present in 55.7% of subjects and 95 women (13.7%) had at least one severe fracture. The women with trochanteric hip fracture showed higher SDI and higher prevalence of diabetes with respect to those with cervical hip fracture, p=0.017 and p=0.001, respectively. SDI, surgical menopause, family history of fragility fracture, and type2 diabetes mellitus were independently associated with the risk of trochanteric hip fracture. Moreover, a higher SDI was associated with a higher percentage of post-surgery complications (p=0.05) and slower recovery (p<0.05). CONCLUSIONS: Our study suggests that the burden of prevalent vertebral fractures is more strictly associated with the trochanteric than the cervical localisation of hip fracture and that elevated values of SDI negatively influence short term functional outcomes in women with hip fracture.

Feasibility of quantitative ultrasound measurements on the humerus of newborn infants for the assessment of the skeletal status.

Quantitative ultrasound (QUS), although widely used in adults has, so far, been scarcely employed in newborn infants and children. This study aimed to evaluate the feasibility of the use of QUS in newborn children and the factors influencing QUS parameters. In 140 consecutive healthy full-term newborn babies (76 male and 64 female; gestational age: 39.5 +/- 1.5 weeks) QUS parameters were assessed within 3 days of the child's birth at the distal diaphysis of the humerus by use of Bone Profiler, after an appropriate modification of caliper and software. In all subjects we evaluated the amplitude-dependent speed of sound (AD-SoS) (meters per second), the characterizing graphic trace parameters [signal dynamic (SDy), fast wave amplitude (FWA) and bone transmission time (BTT)], SoS (meters per second), that is, the speed of sound calculated on the first peak, and hBTT, that is, the interval time between the first peak of the ultrasound and when this reaches the speed of 1,570 m/s, which is the velocity of ultrasound in the soft tissue. This latter parameter allows one to measure bone tissue independently of soft tissue. QUS measurements were also performed at the phalanges on all mothers (age range 24-38 years), who also completed a self-report questionnaire on their obstetric history, smoking and dietary habits and family history of osteoporosis. In 73 mothers and their children QUS was repeated after 12 months. All QUS parameters were slightly higher in male than in female newborn infants but the difference was not significant. BTT and hBTT of neonates showed a significant relationship with birth weight (r = 0.20; P < 0.05 and r = 0.37; P < 0.01, respectively) and with cranial circumference (r = 0.22; P < 0.05 and r = 0.36; P < 0.01, respectively). In newborn infants none of the QUS parameters was significantly influenced by maternal QUS or by maternal smoking and calcium intake. In a model of multiple regression analysis the cranial circumference was the only parameter entered into the model, explaining approximately 15% of hBTT value. At month 12 AD-SoS and SoS were slightly lower than at birth (-11% and -0.1%, respectively), whereas both BTT and hBTT showed a significant (P < 0001) increase. The present study demonstrated the feasibility of the use of QUS, as assessed by a new measurement approach at the humerus, in the evaluation of skeletal status in neonates. BTT and, above all, hBTT, appears to be the best parameter for both evaluation of skeletal status at birth and monitoring of bone growth in the first year of life.

The use of ultrasound in the assessment of bone status.

The assessment of skeletal status has wide clinical applications, especially in the management of osteoporosis. Osteoporosis, once thought of as an unpreventable and untreatable aging process, has revealed many of its secrets over the last decade, and the advent of successful drug therapy has changed our perception of the disease. Non-invasive techniques play a fundamental role in the diagnosis of osteoporosis and in the assessment of the efficacy of drug treatments. The primary technique used in osteoporosis is dual X-ray absorptiometry (DXA), that has been established as a reliable means of measuring bone density. Quantitative ultrasound (QUS), because of the relative portability of the equipment, ease of use, lack of ionizing radiation and low cost, has great potential for widespread use. Five devices for QUS assessment have recently been approved by the Food and Drug Administration and many more applications are in progress. QUS is a relatively new technology, at least in its application to bone fragility. Nevertheless, QUS has demonstrated that it is able to detect bone fragility as well as DXA. However, diagnosis of osteoporosis by QUS remains contentious, but the problems are due more to the limitations of the present T-scores rather than to the technique. A better option for QUS would be to report results in terms of remaining lifetime fracture risk, keeping in mind that a risk estimate needs not only the QUS or DXA measurement, but also the specific data, such as age, weight, gender, hormonal status and fracture history of the patient.

Validation of a food frequency questionnaire for nutritional calcium intake assessment in Italian women.

OBJECTIVE: To evaluate a food frequency questionnaire assessing calcium intake in women. DESIGN: : Estimates of calcium intake from the food frequency questionnaire were compared with those from 14 day records from 206 Caucasian women aged 25-75 y in Siena, Italy. SUBJECTS: Subjects were randomly recruited from the residents list of the city of Siena, Italy. Of the 250 initially recruited, 39 did not meet the inclusion criteria or failed to complete the diet record and five outliers were excluded before the statistical analysis on the basis that their diet record was unlikely to represent habitual intake. RESULTS: Mean dietary calcium intakes were 829+/-255 (s.d.) mg/day from the questionnaire and 818+/-260 (s.d.) mg/day from the diet record. The mean difference in intake by the two methods (-11.3+/-116.4 mg/day) did not differ significantly from zero. Specificity in classifying women consuming less than 800 mg/day calcium was 86.6%, and sensibility in classifying women consuming more than 800 mg/day calcium was 89.4%. CONCLUSIONS: The food frequency questionnaire could be used in epidemiological studies to assess calcium intake in young to elderly women. The specificity in identifying low calcium intake subjects makes it useful also as an educational tool in diet counselling and for prescribing calcium supplementation.

Quantitative ultrasound in the assessment of skeletal status in uremic patients.

Renal osteodystrophy (ROD) can be characterized by both high (HT) and low (LT) bone turnover states. Although bone biopsy remains the "gold standard" to diagnose ROD, noninvasive tools for the diagnosis and follow-up of such bone disease are desirable. Recently, ultrasound (US) techniques, proposed to assess skeletal status, have been shown to be correlated not only with bone density but also with bone quality. We have investigated 98 patients on chronic hemodyalisis (HD) and 98 healthy, sex- and age-matched subjects. Amplitude-dependent speed of sound (AD-SOS) and ultrasound bone profile score (UBPS) at phalanxes and speed of sound (SOS), broadband ultrasound attenuation (BUA), and a quantitative ultrasound index (QUI/stiffness) at the heel were performed in both groups. In all subjects intact parathyroid hormone (PTH), total alkaline phosphatase (T-ALP), bone isoenzyme alkaline phosphatase (B-ALP), and carboxy-terminal telopeptide of type I collagen (ICTP) were assessed. All US parameters were significantly lower in the hemodialysis group than in control subjects. Moreover, among US parameters only AD-SOS and UBPS showed a significant correlation with PTH, T-ALP, and B-ALP. Dialytic age showed a modest, but significant correlation only with US parameters at the phalanxes. On the basis of bone biochemical markers, we considered a group with high and a group with normal to low bone turnover. AD-SOS and UBPS, but not SOS, BUA, and stiffness were significantly (p < 0.01) lower in the high bone turnover than in low bone turnover group. Furthermore, in the high bone turnover group, parameters of the US phalanxes strongly correlated with B-ALP. Our results seem to demonstrate that US parameters are a useful tool in the assessment of skeletal status in patients on maintenance dialysis.

Ultrasonographic assessment of bone in normal Italian males and females.

Recently ultrasound techniques have been proposed to evaluate skeletal status. Speed of sound and attenuation through the bone are the ultrasound properties currently used to assess bone strength and fragility. The speed of sound in m s-1 (SOS), broadband ultrasound attenuation in dB MHz-1 (BUA) and stiffness (S) in 134 healthy females (age range 10-90 years) and in 100 healthy males (age range 10-93 years) was measured using the Achilles scanner (Lunar Corp., Madison, WI, USA). A polynomial function was applied to the observed data to evaluate a pattern of age-related BUA, SOS and S changes. Peak values of SOS, BUA and S were reached in both sexes at the age of 30 years. Average decreases of 12.9% in BUA, 4.9% in SOS and 28.9% in S were found in men aged between 30 and 90 years. In women average decreases of 17.2% in BUA, 4.2% in SOS and 31.9% in S were discovered in those aged between 30 and 90 years. The analysis of SOS, BUA and S changes between pre- and post-menopausal women revealed a significant decrease of these parameters with years since menopause. These data indicate an age-related decrease of ultrasound signals in both sexes. Furthermore, this technique is able to detect, in females, menopause related changes due to oestrogen failure. In contrast, in males, the age-related loss of ultrasound signals appears to be more linear.