Is it time to consider population screening for fracture risk in postmenopausal women? A position paper from the International Osteoporosis Foundation Epidemiology/Quality of Life Working Group.

The IOF Epidemiology and Quality of Life Working Group has reviewed the potential role of population screening for high hip fracture risk against well-established criteria. The report concludes that such an approach should strongly be considered in many health care systems to reduce the burden of hip fractures. INTRODUCTION: The burden of long-term osteoporosis management falls on primary care in most healthcare systems. However, a wide and stable treatment gap exists in many such settings; most of which appears to be secondary to a lack of awareness of fracture risk. Screening is a public health measure for the purpose of identifying individuals who are likely to benefit from further investigations and/or treatment to reduce the risk of a disease or its complications. The purpose of this report was to review the evidence for a potential screening programme to identify postmenopausal women at increased risk of hip fracture. METHODS: The approach took well-established criteria for the development of a screening program, adapted by the UK National Screening Committee, and sought the opinion of 20 members of the International Osteoporosis Foundation's Working Group on Epidemiology and Quality of Life as to whether each criterion was met (yes, partial or no). For each criterion, the evidence base was then reviewed and summarized. RESULTS AND CONCLUSION: The report concludes that evidence supports the proposal that screening for high fracture risk in primary care should strongly be considered for incorporation into many health care systems to reduce the burden of fractures, particularly hip fractures. The key remaining hurdles to overcome are engagement with primary care healthcare professionals, and the implementation of systems that facilitate and maintain the screening program.

Long-term treatment of osteoporosis in postmenopausal women: a review from the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) and the International Osteoporosis Foundation (IOF).

INTRODUCTION: Postmenopausal osteoporosis is a chronic disease requiring treatment that balances long-term fracture efficacy against risk. METHODS: We reviewed the efficacy and safety of calcium and vitamin D, the selective estrogen receptor modulators (SERMs), the bisphosphonates, denosumab, and strontium ranelate in studies of 3 years or longer. RESULTS: Six trials lasted for 5 years, and seven went beyond that. The evidence beyond 5 years is generally weak, mainly due to methodological issues (open-label design, small samples, or absence of placebo control). Although calcium and vitamin D appear to be beneficial, the data are insufficient to evaluate benefits and risk beyond 3 years. The fracture efficacy of SERMs beyond 5 years is not known, though increases in bone mineral density (BMD) appear to be maintained. The SERMs have good long-term safety, including protective effects against breast cancer. The bisphosphonates have established fracture efficacy to 3 years, and 4 or 5 years with alendronate and risedronate. The evidence beyond 5 years indicates sustained increases in BMD. The safety of the bisphosphonates does not appear to be modified with time, with the possible exceptions of atypical subtrochanteric fracture and other events of unknown frequency. Denosumab has been tested up to 5 years, with continued increased in BMD and no reported safety issues. There is evidence for fracture efficacy of strontium ranelate, and sustained increases in BMD over 10 years. Strontium ranelate has good long-term safety. CONCLUSION: Robust long-term studies are relatively rare for the osteoporosis treatments, and generally show maintenance of BMD and, for some agents, an additional reduction in fracture incidence.

Idiopathic juvenile osteoporosis--an analysis of the muscle-bone relationship.

INTRODUCTION: Idiopathic Juvenile Osteoporosis (IJO), a disease of unknown etiology, manifests typically by pain, bone deformities and fractures. Due to limits in BMD data interpretation, evaluation of the muscle-bone functional unit has recently been proposed as a means to assess the general competence of the skeleton. The aim of this study was to evaluate skeletal status during the acute phase of IJO and during recovery from the disease in relation to muscles. MATERIALS AND METHODS: The study population comprised 61 IJO children, including 34 girls (mean age: 13.6+/-3.1 years; range: 7-18) and 27 boys (14.3+/-3.3; 5-18 years). DXA total body (TB) and lumbar spine (S) bone mineral content (BMC) and density (BMD) were measured. Lean body mass (LBM) was employed to calculate SBMC/LBM, TBBMC/LBM, body height (BH)/LBM and LBM/body weight (BW) ratios. Previously established references for healthy controls were utilized for the calculation of Z-score values in IJO cases in respect to phase of the disease. RESULTS: IJO patients had significantly decreased Z-score values for TBBMD, SBMD, SBMC/LBM and TBBMC/LBM ratios but not for the LBM and BH/LBM or LBM/BW ratios. During the acute phase IJO girls had mean Z-scores for TBBMD and SBMD of -2.49+/-0.61 and -3.27+/-1.03, respectively, which were significantly lower than Z-scores during the recovery phase: -0.90+/-0.66, -1.38+/-0.95 (p<0.0001). IJO boys during the acute phase had Z-scores of -2.08+/-0.65 and -2.75+/-1.19 for TBBMD and SBMD, respectively, which were significantly lower than those during the recovery phase (-0.51+/-1.04 and -1.39+/-1.49; p<0.0001). Further, during the acute phase, TBBMC/LBM Z-scores of -2.95+/-1.15 and -2.56+/-1.49 were noted in girls and boys, respectively; the corresponding SBMC/LBM Z-scores were -2.66+/-1.07 and -2.22+/-1.62. During the recovery from IJO, TBBMC/LBM and SBMC/LBM Z-scores of -1.07+/-0.99 and -0.91+/-1.16 and of -1.15+/-1.40 and -0.68+/-1.45 were noted in girls and boys, respectively, and all were significantly higher than those during the acute phase (p<0.0001). CONCLUSIONS: The results of this study indicate that IJO is a bone disorder characterized by an imbalanced muscle-bone relationship and fractures at onset and during the acute phase and by at least a partial recovery without bone pain and new fractures. Implementation of the BH/LBM, TBBMC/LBM and SBMC/LBM ratios to the armamentarium of pediatricians diagnosing bone disorders will provide mechanically meaningful data for diagnostic purposes and, hopefully, for proper therapeutic decisions.

Efficacy and safety of ibandronate given by intravenous injection once every 3 months.

Oral bisphosphonates are established therapeutics for postmenopausal osteoporosis. Alternative, simplified dosing regimens that improve tolerability and promote convenience may be advantageous. Ibandronate is a highly potent, nitrogen-containing bisphosphonate that can be administered as a convenient intravenous (i.v.) injection (over 15-30 s) in schedules featuring extended between-dose intervals. In a recent fracture prevention study, 1 and 0.5 mg i.v. ibandronate injections, given once every 3 months, were shown to dose-dependently increase lumbar spine and hip bone mineral density (BMD) and decrease biochemical markers of bone turnover in women with postmenopausal osteoporosis, but the overall magnitude of efficacy provided by both doses was suboptimal. In the present study (Intermittent Regimen intravenous Ibandronate Study: the IRIS study), the dose-response relationship with intermittent intravenous ibandronate injections was further evaluated in 520 postmenopausal osteoporotic women (aged 55-75 years, time since menopause >or= 5 years, lumbar spine [L1-L4] BMD T score < -2.5). At enrolment, participants were randomized to receive either 2 mg (n = 261) or 1 mg (n = 131) ibandronate or placebo (n = 128) intravenous injections, given once every 3 months. After 1 year, ibandronate therapy produced substantial and dose-dependent increases in lumbar spine and hip BMD, and decreases in biochemical markers of bone turnover, with the 2 mg dose providing significantly greater efficacy than the 1 mg dose. Most notably, lumbar spine BMD increased by 5.0% and 2.8% in the 2 and 1 mg groups, respectively, and decreased by 0.04% in the placebo group. Furthermore, total hip BMD increased by 2.9%, 2.2%, and 0.6%, respectively. Serum and urinary CTX, reflecting bone resorption, were decreased by 62.5% and 61%, respectively, with the 2 mg dose, and by 43.5% and 42%, respectively, with the 1 mg dose. Intravenous ibandronate was well tolerated with a similar incidence of adverse events to placebo. Importantly, no indicators of renal toxicity were reported. In summary, the 2 mg ibandronate regimen provides significantly greater BMD increases and significantly greater suppression of bone resorption markers than the 1 mg dose used in this study and in the previous fracture prevention study. Ongoing studies aim to further establish the efficacy and convenience of intermittent intravenous ibandronate injections in postmenopausal osteoporosis.

[Progress in measurement of the calcaneus using ultrasonic methods in children and adolescents]. / Postepy w pomiarach kosci pietowej ilosciowa metoda ultradzwiekowa u dzieci i mlodziezy.

At present, Dual Energy X-ray Absorptiometry (DEXA) method is a reference method to diagnose osteoporosis. This method allows to measure bone density and bone mass, however bone quality can not be estimated. Quantitative ultrasound (QUS) method provides information about bone structure. The aim of our work was the evaluation of QUS method in healthy children, establishing reference values in cross-sectional study of healthy children aged 7-18 yrs and to examine the annual change of ultrasound parameters in prospective study at pubertal. Group of 530 girls and 369 boys was recruited from Warsaw schools, and right heel was measured with Achilles Plus apparatus. Measurements were repeated after 1 year, in a subgroup of 153 children aged 9-13 yrs. The method was adapted for paediatric measurements by using limiter of ultrasonic wave and pads for positioning foot in water chamber. Speed of sound (SOS) and broadband ultrasound attenuation (BUA) were measured and Stiffness index was calculated. Width of heel, at the same location as QUS measurement, was also measured using calipers. SOS, BUA and Stiffness values increased by age in boys and girls. BUA and Stiffness values were significantly higher in 15, 16 and 17 year old boys than in age-matched girls (in 18 yrs--only Stiffness). However, there were no significant sex differences in annual increase of SOS, BUA and Stiffness, although the biggest increase was observed between the age of 13-14 yrs for boys and 11-12 yrs for girls. That may reflect pubertal spurt of body growth but that relationship was not confirmed by annual increases calculated from cross-sectional data. Statistically significant correlation of SOS, BUA and Stiffness with body mass, height, body mass index (BMI) and heel width was observed. Normalization of SOS, BUA and Stiffness on heel width decreased force of that correlation but it was still statistically significant. Dynamics of SOS, BUA and Stiffness increase by age was higher in boys than in girls. This phenomenon is probably related to higher peak bone mass in men than in women, and lower risk of fracture in men, especially concerning hip. Increase of speed of sound, broadband ultrasound attenuation and stiffness index by age, and their correlations with body mass, height and body mass index reflects bone growth in children and adolescents. Broadband ultrasound attenuation and Stiffness index show sex differences in bone development in adolescence. Higher dynamics of the increase of speed of sound, broadband ultrasound attenuation and Stiffness index by age in boys confirms faster bone mass accumulation in boys than in girls.

[Osteoporosis in children]. / Osteoporoza u dzieci.

Osteoporosis is defined as a bone disorder with low bone mass and altered bone quality leading to fractures. In adult patients as a reference point for its diagnosis peak bone mass reached in second decade of life is utilized. In children the mean values of age matched control group are used as a reference point for diagnosis of osteoporosis. As a critical value two standard deviations below the reference values of the control group in children are used. Interpretation of the densitometric measurements in children is more complicated than in adults because of heterogeneity of the skeleton and continuous growth of children. Obtained results are affected by age, sex, body mass, height, bone age, environmental factors and illnesses. Osteoporosis in children is observed primary symptom in osteogenesis imperfecta and idiopathic juvenile osteoporosis.

Hip geometry, bone mineral distribution, and bone strength in European men and women: the EPOS study.

Hip geometry and bone mineral density (BMD) have been shown previously to relate, independently of each other, to risk of hip fracture. We used Lunar DPX "beta" versions of hip strength analysis (HSA) and hip axis length (HAL) software to analyze scans from ten representative age-stratified population samples in the European Prospective Osteoporosis Study (EPOS). All 1617 subjects were >50 years of age, and 1033 were women. The data were modeled with gender and center as categorical variables. The bone mineral density of the upper half of the femoral neck declined at a faster rate with age than that in the lower half. Femoral neck cross-sectional moment of inertia (CSMI), a measure of resistance to bending, showed no significant age reduction in either gender. However, height and weight effects on CSMI were significantly more beneficial in men than in women (0.002 < p < 0.012) and the weight effect appeared to be mediated by bone mineral content (BMC). Compressive stress (Cstress), defined as the stress in the femoral neck at its weakest cross section arising from a standardized fall, was higher in women. Although Cstress increased with body weight when BMC was held constant, in practice it fell through the association and statistical interaction of rising body weight with rising BMC. HAL, as expected, was strongly positively associated with male gender and also height (p < 0.0001). Hip strength-related indices were markedly center-dependent. Significant differences (p < 0.0001) were noted between the centers for all the variables investigated that related to hip geometry. Adjustment for femoral neck bone mineral content (totBMC) showed these center differences to account for >50% of center variation in hip strength, which remained highly significant (p < 0.0001). We conclude that there are substantial geographical differences in femoral neck geometry as well as in BMD. These geometric variations may contribute to the large variations in hip fracture risk across Europe. The effects of aging on hip strength need to be explored in longitudinal studies.

[Indices of mechanical strength of the distal radius in healthy women and women with Colles fracture]. / Wskazniki wytrzymalosci mechanicznej dystalnego odcinka kosci promieniowej u kobiet zdrowych i ze zlamaniem typu Collesa.

Wrist fractures (Colles) are one of the most frequently observed osteoporotic fractures in postmenopausal women. The aim of our study was the comparison of mechanical properties of distal radius of women with Colles fracture using a Stratec XCT 960 peripheral quantitative computed tomography (pQCT) in relation to age-pair controls without a wrist fracture. Using the pQCT method for estimation of SSI (Strength Strain Index), we found significant differences of SSI values in Colles subjects. In clinical practice, pQCT offers new diagnostic tools which cannot be provided by conventional densitometric methods.

[Age-related changes of densitometric and strength parameters evaluated with QCT method in healthy women]. / Zwiazane z wiekiem zmiany wartosci parametrów densytometrycznych i wytrzymalosciowych wyznaczonych u zdrowych kobiet metoda pQCT.

In the present study the age-related changes of pQCT values in normal Polish women were examined. The volumetric bone mineral density, trabecular density, cortical density and Strength Strain Index was measured using peripheral quantitative computed tomography (Stratec XCT 960) in 459 healthy women aged 18-60 years. Bone mineral measurement of the distal and proximal radius may be useful in evaluation of age-related bone loss, fracture risk and for diagnosis of osteoporosis.

[The influence of the height of body mass on ultrasound measurements of bones in healthy Polish women]. / Wplyw wzrostu i masy ciala na wartosci parametrów ultradzwiekowych kosci u zdrowych kobiet polskiej populacji.

Broadband ultrasound attenuation (BUA) and speed of sound (SOS) and stiffness index of the os calcis were measured in a sample of 407 normal sedentary women aged 40-60 years. Achieved results deliver reference data supporting measurement interpretation of physiologic as well pathologic conditions. Correlations were performed between ultrasound measurements and antropometric data. We observed that in women over 55 years there is a significant age related decline of BUA, SOS and stiffness. Significant correlations were also stated (p < 0.05) between body mass of woman aged 40-45, 46-50 i 51-55 and ultrasonic parameters of broadband ultrasound attenuation (BUA) (r = 0.26, 0.46, 0.43 respectively), considered as related to internal trabecular bone structure. In group of eldest woman (aged 56-60) such a correlations were not present, probably as an effect of intensive bone loss related to lack of protective effect of estrogens.

[Genetic factors in osteoporosis]. / Czynniki genetyczne w osteoporozie.

Osteoporosis is a widespread disease affecting more than 1/4th of the female and 1/10th of the male population. It is characterised by a low bone mass, which in turn leads to osteoporotic fractures. Bone mass can be described as bone mineral density (BMD). BMD in human population is subject to quite significant interpersonal variability, for 75 to 80% of which, the genetic factors are responsible. To investigate the dependence of BMD on genetic factors, a possible links between the BMD and the natural polymorphism of so called "candidate genes" are checked. The first candidate gene to be investigated was the gene coding for the receptor of the active form of vitamin D. A statistical linkage between the naturally occurring polymorphism of that gene and the BMD was found by many research centres. It was found that certain polymorphic variants of that gene are linked to higher BMD's than the other ones. This trend existed in different human races and various age groups in many countries including Poland. A batch of negative results which appeared in some papers can be explained either by high calcium consumption in the given population, or the existence of another gene affecting bone metabolism and closely coupled to the vitamin D receptor gene. Other investigated and promising genes are the genes coding for other receptors (e.g. oestrogen), regulatory proteins (e.g. IL-6) and structural proteins (e.g. type I collagen).

[Calcitonin -- 1998]. / Kalcytonina--1998.

Calcitonin is one of three most important factors involved in the regulation of systemic calcium homeostasis. Since its discovery in 1961 the structure of calcitonin from different species including human was established, synthetized and developed for use in human clinic. Up to now calcitonin is utilized in treatment of hypercalcemia, Paget disease, algodystrophy, primary and secondary osteoporosis and analgesia. Beside comparative studies aiming on selection of the most effective protocol of treatment and utilization, lately calcitonin is extensively studies for its antifracture potency in osteoporosis. One of the substantial therapeutical progress also appeared the utilization of intransal preparation of calcitonin.

[Usefulness of bone densitometry, quantitative computed tomography and quantitative ultrasound in diagnosis and monitoring of osteoporosis treatment]. / Przydatnosc badan densytometrycznych, ilosciowej tomografii komputerowej oraz technik ultradzwiekowych w diagnostyce i monitorowaniu leczenia osteoporozy.

Bone densitometry is characterized by high sensitivity and specificity in osteoporosis, and new generations of densitometers enable measurements with improved intra- and inter-assay precision. The clinical potential of bone densitometry is well documented and the technique is widely used in clinical practice. It does not, however, allow for measurement of "true" bone density; instead it measures so called serial density (expressed in g/cm2) which is the distribution of bone mass over the flat projection of the skeleton. Limitations of densitometric techniques can be overcome by applying other methods, i.e. quantitative computed tomography (QCT) and ultrasound (US). QCT enables separate measurements of compact and trabecular bone density (expressed in g/cm3), as well as calculation of Strength-Strain Index (SSI), reflecting the mechanical resistance of bone to fracture. US is a non-invasive technique, providing information of fracture risk and bone tissue quality. Both techniques seem very promising and have been extensively studied recently; they are expected to move from clinical research to clinical practice soon.

Pyridinium crosslinks of collagen as a marker of bone resorption rates in children and adolescents: normal values and clinical application.

The aim of our study was to establish normal values of urinary pyridinoline (Pyr) and deoxypyridinoline (DPyr) excretion for children aged 3-18 years, examine the biological variability of the marker, and assess its clinical value for pediatric patients with growth hormone deficiency. Pyr and DPyr was measured in first void urine samples from 692 healthy subjects (340 boys, 352 girls) by high-performance liquid chromatography. At sampling, age, body height, and weight was recorded for all individuals. Short-term variability in crosslinks excretion was examined in four healthy children. The clinical value of the marker was studied in seven patients with growth hormone (GH) deficiency. In childhood, crosslinks excretion exceeded normal adult values by about fivefold and declined during puberty. In the age range of 13-18 years, gender-related differences in Pyr and DPyr levels were observed, presumably resulting from the earlier onset of puberty in girls. Urinary levels of Pyr and DPyr were highly correlated both in males and females. Pyr/DPyr ratio was significantly higher in adolescents than children, suggesting enhanced release of Pyr from extraosseous sources. In both genders, neither age nor anthropometric variables showed a linear effect on crosslinks excretion. The range of within-subject, short-term variability in urinary Pyr and DPyr was relatively high (CV: 6%-21%), indicating that single measurements of crosslinks excretion may not adequately reflect bone resorption rates in children. Pyr and DPyr levels were significantly lower in GH-deficient patients and normalized during human growth hormone (hGH) therapy. Significant correlations between growth velocity (GV) and crosslinks levels were found, but individual prediction of GV increment during hGH treatment may be inaccurate. Pyr/DPyr ratio was not related to GV. It is concluded that measurement of urinary Pyr and DPyr excretion in children may be a valuable tool to assess bone resorption rates in population-based studies. In individual patients, however, only qualitative evaluation of disease severity and response to treatment seems justified.

Collagen peptides in osteogenesis imperfecta, idiopathic juvenile osteoporosis and Ehlers--Danlos syndrome.

We evaluated the potential of the carboxy-terminal propeptide of type I procollagen (PICP), the carboxy-terminal telopeptide of collagen I (ICTP), and the amino-terminal propeptide of type III procollagen (PIIINP) to differentiate osteogenesis imperfecta (OI) from Ehlers-Danlos syndrome (EDS) and idiopathic juvenile osteoporosis (IJO) in paediatric patients. Markedly decreased serum concentrations of PICP were found in type I OI, while in IJO they were much less diminished, and in EDS they were near to normal. In type III and IV OI, the serum PICP level was lowered in prepubertal patients, whereas at puberty it was comparable to that in controls. Serum ICTP and PIIINP levels in patients with OI did not differ significantly from the levels in EDS and IJO. Measurements of serum PICP levels seem to be useful in discriminating OI from EDS and IJO in prepubertal children. In pubertal children, however, they lose their diagnostic power.

[Pediatric aspects of osteoporosis]. / Pediatryczne aspekty osteoporozy.

The skeleton is not a single entity; the age of onset, rate of accrual and age of attainment of peak bone density vary according to gender and according to region. Exposure of life style factors during growth and disease may produce site specific deficits in bone density in adulthood. Since bone mass in the elderly depends beside the rate of involutional bone loss mainly on the peak bone mass its optimal development in childhood and adolescence appears as being the key issue problem in prophylactic strategy of osteoporotic therapy.

[Measurements of calcaneus bone density by ultrasonography in children and adolescents]. / Pomiary gestosci kosci pietowej metoda ultrasonograficzna u dzieci i mlodziezy.

In recent years the interest in growing in the use of ultrasonographic method for the assessment of bony tissue density. However, studies using this method were conducted almost exclusively in adult patients. The aim of this study was to apply this method for measurements in children in wide age range (7-18 years) and to determine value range of the parameters SOS, BUA and Stiffness for children in Warsaw in age and sex groups. The studies included 233 children of either sex, aged 7-18 years, healthy on medical examination coming from Warsaw schools. Achilles (Lunar Corp. WI, USA) bone densitometer was used with producer's software, 1.5c version. During examination with the Achilles device, the velocities of ultrasound beam passage through the calcaneus (SOS m/s) and the damping factor of ultrasound wave depending on its frequency (BUA db/MHz) were measured. Additionally the so called "stiffness factor" was calculated. The Achilles device was adapted for measurements in children reducing the diameter of the measuring beam to 1 cm and using pads positioning the child's foot in the device. Equal increase of SOS, BUA and Stiffness parameters with age was observed with the exception of the SOS parameter in girls which increased intensively from 7 to 12 years of age while over 12 years of age its increase was slight. Using linear regression analysis it was found that the values of SOS, BUA and Stiffness parameters depended directly proportionally on age, body weight and height. Respective correlation factors (r) were from 0.49 (body weight-SOS to 0.80 (height-BUA). The observed dependence of the SOS, BUA and Stiffness parameters on body weight, height and especially age enables presuming that the results of calcaneus density measurements by ultrasonographic method reflect the skeletal development in children.

[Quantitative computerized tomography of peripheral body parts (pQCT)--results of measurements in healthy women from the Polish population]. / Ilosciowa tomografia komputerowa obwodowych czesci ciala (pQCT)-- wyniki pomiar-ow u zdrowych kobiet w populacji Polskiej.

The authors present a new method in densitometry-quantitative computerized tomography of peripheral body parts (pQCT). It takes into account the volume of measured bones expressing the results as density in physical sense, and makes possible differentation of internal bone structure with a very low exposure (up to 6 mrem for a complete measurement). The authors have begun also work on gathering reference data for the Polish population and they present the preliminary results of measurements in an initial group of 97 women.

[Comparison of bone density in various skeletal parts in women during peri and postmenopause with previous Colles fracture]. / Porównanie gestosci masy kostnej w róznych miejscach szkieletu u kobiet w okresie peri i postmenopauzalnym z przebytym zlamaniem Collesa.

Forearm fracture of Colles type is one of the most frequently observed osteoporotic fractures in women in postmenopausal period. It is proved that the group of women who had Celles fractures (n = 63) has lower bone mineral density in all measured sites except hip comparing to the controls (n = 53). Osteopenia found involves trabecular bone. Women with previous forearm fracture can be treated as the group of increased risk for spine and femoral neck fracture in the future.