Optimisation of vitamin D status in global populations.

Vitamin D is important for musculoskeletal health. Concentrations of 25-hydroxyvitamin D, the most commonly measured metabolite, vary markedly around the world and are influenced by many factors including sun exposure, skin pigmentation, covering, season and supplement use. Whilst overt vitamin D deficiency with biochemical consequences presents an increased risk of severe sequelae such as rickets, osteomalacia or cardiomyopathy and usually warrants prompt replacement treatment, the role of vitamin D supplementation in the population presents a different set of considerations. Here the issue is to keep, on average, the population at a level whereby the risk of adverse health outcomes in the population is minimised. This position paper, which complements recently published work from the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases, addresses key considerations regarding vitamin D assessment and intervention from the population perspective. This position paper, on behalf of the International Osteoporosis Foundation Vitamin D Working Group, summarises the burden and possible amelioration of vitamin D deficiency in global populations. It addresses key issues including screening, supplementation and food fortification.

Profile of patients who visit medical internists for an osteoporosis assessment: The OSTEOMED registry. / Perfil de los pacientes que acuden al médico internista para valoración de osteoporosis: registro OSTEOMED.

BACKGROUND AND OBJECTIVES: Osteoporosis is considered a generalised skeletal disorder in which there is impaired bone resistance, which predisposes the individual to a greater risk of fracture. The aim of this cross-sectional study was to collect and present data on the main clinical characteristics of patients who consult medical internists in Spain. Understanding these characteristics can help in implementing action plans to improve these patients' care more effectively and efficiently. MATERIAL AND METHODS: Through an analysis of the Osteoporosis in Internal Medicine (OSTEOMED) registry, this study presents the main clinical characteristics of patients with osteoporosis who attended internal medicine consultations in 23 Spanish hospital centres between 2012 and 2017. We analysed the reasons for the consultations, the densitometric values, the presence of comorbidities, the prescribed treatment and other lifestyle-related factors. RESULTS: In total, 2024 patients with osteoporosis were assessed (89.87% women, 10.13% men). The patients' mean age was 64.1±12.1 years (women, 64.7±11.5 years; men, 61.2±14.2 years). There was no significant difference between the sexes in their history of recent falls (9.1% and 6.7%); however, there were significant differences in the daily intake of calcium from milk products (553.8±332.6mg for women vs. 450.2±303.3mg for men; P<.001) and in the secondary causes of osteoporosis (13% of men vs. 6.5% of women; P<.001). In the sample, there were 404 fractures (20%), with a notable number of confirmed vertebral fractures (17.2%, 35.6% in men vs. 15.2% in women; P<.001). A large portion of the patients did not undergo the indicated treatment and presented low levels of physical activity and sun exposure. A significant percentage of the patients presented associated comorbidities, the most common of which were hypertension (32%) and dyslipidaemia (28%). CONCLUSIONS: These results define the profile of patients with osteoporosis who attend internal medicine consultations in Spain. The results also show the multisystemic character of this condition, which, along with its high prevalence, determine that the specific internal medicine consultations dedicated to managing the condition are the appropriate place for caring for these patients.

Standardising the descriptive epidemiology of osteoporosis: recommendations from the Epidemiology and Quality of Life Working Group of IOF.

UNLABELLED: The Committee of Scientific Advisors of International Osteoporosis Foundation (IOF) recommends that papers describing the descriptive epidemiology of osteoporosis using bone mineral density (BMD) at the femoral neck include T-scores derived from an international reference standard. INTRODUCTION: The prevalence of osteoporosis as defined by the T-score is inconsistently reported in the literature which makes comparisons between studies problematic. METHODS: The Epidemiology and Quality of Life Working Group of IOF convened to make its recommendations and endorsement sought thereafter from the Committee of Scientific Advisors of IOF. RESULTS: The Committee of Scientific Advisors of IOF recommends that papers describing the descriptive epidemiology of osteoporosis using BMD at the femoral neck include T-scores derived from the National Health and Nutrition Examination Survey III reference database for femoral neck measurements in Caucasian women aged 20-29 years. CONCLUSIONS: It is expected that the use of the reference standard will help resolve difficulties in the comparison of results between studies and the comparative assessment of new technologies.

Maintenance of antifracture efficacy over 10 years with strontium ranelate in postmenopausal osteoporosis.

UNLABELLED: In an open-label extension study, BMD increased continuously with strontium ranelate over 10 years in osteoporotic women (P < 0.01). Vertebral and nonvertebral fracture incidence was lower between 5 and 10 years than in a matched placebo group over 5 years (P < 0.05). Strontium ranelate's antifracture efficacy appears to be maintained long term. INTRODUCTION: Strontium ranelate has proven efficacy against vertebral and nonvertebral fractures, including hip, over 5 years in postmenopausal osteoporosis. We explored long-term efficacy and safety of strontium ranelate over 10 years. METHODS: Postmenopausal osteoporotic women participating in the double-blind, placebo-controlled phase 3 studies SOTI and TROPOS to 5 years were invited to enter a 5-year open-label extension, during which they received strontium ranelate 2 g/day (n = 237, 10-year population). Bone mineral density (BMD) and fracture incidence were recorded, and FRAX® scores were calculated. The effect of strontium ranelate on fracture incidence was evaluated by comparison with a FRAX®-matched placebo group identified in the TROPOS placebo arm. RESULTS: The patients in the 10-year population had baseline characteristics comparable to those of the total SOTI/TROPOS population. Over 10 years, lumbar BMD increased continuously and significantly (P < 0.01 versus previous year) with 34.5 ± 20.2% relative change from baseline to 10 years. The incidence of vertebral and nonvertebral fracture with strontium ranelate in the 10-year population in years 6 to 10 was comparable to the incidence between years 0 and 5, but was significantly lower than the incidence observed in the FRAX®-matched placebo group over 5 years (P < 0.05); relative risk reductions for vertebral and nonvertebral fractures were 35% and 38%, respectively. Strontium ranelate was safe and well tolerated over 10 years. CONCLUSIONS: Long-term treatment with strontium ranelate is associated with sustained increases in BMD over 10 years, with a good safety profile. Our results also support the maintenance of antifracture efficacy over 10 years with strontium ranelate.

Health-related quality of life of X-linked hypophosphatemia in Spain.

BACKGROUND: Health-related quality of life (HRQoL) of patients with X-linked hypophosphatemia (XLH) is lower than that of both the general population and the patients with other chronic diseases, mainly due to diagnostic delay, treatment difficulties, poor psychosocial support, and problems with social integration. Early diagnosis and optimal treatment are paramount to control the disease in patients with XLH, avoid complications, and maintain or improve their HRQoL. We, therefore, analyzed the HRQoL of pediatric and adult patients with XLH treated with conventional therapy in Spain. RESULTS: We used several versions of the EuroQol-5 dimensions (EQ-5D) instrument according to the age of patients with XLH. Then we compared the HRQoL of patients to that of the general Spanish population. Children with XLH (n = 21) had moderate problems in walking about (61.9%), washing or dressing themselves (9.52%), and performing their usual activities (33.33%). They also felt moderate pain or discomfort (61.9%) and were moderately anxious or depressed (23.81%). Adults with XLH (n = 29) had lower HRQoL, with problems in walking (93%, with 3.45% unable to walk independently), some level of pain (86%, with 3.45% experiencing extreme pain), problems with their usual activities (80%) and self-care (> 50%), and reported symptoms of anxiety and/or depression (65%). There were important differences with the general Spanish population. CONCLUSIONS: XLH impacts negatively on physical functioning and HRQoL of patients. In Spanish patients with XLH, the HRQoL was reduced despite conventional treatment, clearly indicating the need to improve the therapeutic approach to this disorder.

X-linked hypophosphatemia (XLH) is a severe inherited disease. It is caused by loss of phosphorus by kidneys. As a result, blood level of phosphorus is low, affectingX-linked hypophosphatemia (XLH) is a severe inherited disease. It is caused by loss of phosphorus by kidneys. As a result, blood level of phosphorus is low, affecting bones and muscles. Patients can have growth retardation, short stature, rickets, limb deformities, pain and other health problems despite traditional treatment. Consequently, their quality of life can be very bad. However, a recently available new treatment (burosumab) can improve this quality of life. We studied the quality of life of children and adults with XLH treated with traditional treatment in Spain. Results showed that children had moderate problems, but adults reported moderate-to-severe problems in walking and performing their usual activities and self-care. Pain and anxiety and/or depression were very frequent. There were important differences with the general Spanish population. Moreover, we also found that XLH is associated to high healthcare cost and even higher socioeconomic cost. Our results highlight the need of improving the treatment of XLH.bones and muscles. Patients can have growth retardation, short stature, rickets, limb deformities, pain and other health problems despite traditional treatment. Consequently, their quality of life can be very bad. However, a recently available new treatment (burosumab) can improve this quality of life. We studied the quality of life of children and adults with XLH treated with traditional treatment in Spain. Results showed that children had moderate problems, but adults reported moderate-to-severe problems in walking and performing their usual activities and self-care. Pain and anxiety and/or depression were very frequent. There were important differences with the general Spanish population. Moreover, we also found that XLH is associated to high healthcare cost and even higher socioeconomic cost. Our results highlight the need of improving the treatment of XLH.

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.

Daily or monthly ibandronate prevents or restores deteriorations of bone mass, architecture, biomechanical properties and markers of bone turnover in androgen-deficient aged rats.

AIM: The aim of this study was to investigate the effects of the bisphosphonate ibandronate (IBN) in a male osteoporosis animal model. METHODS: Two studies were performed in 9-month-old orchidectomised (ORX) or sham-operated rats. In prevention study, subcutaneous IBN was administered daily (1 µg/kg) or monthly (28 µg/kg every 28 days) starting on day of surgery for 5 months. In treatment study, the same treatment started 6 months after ORX. After sacrifice, bone analyses by dual-energy X-ray absorptiometry, 3-dimensional micro-computed tomography, and 3-point bending were performed in femora or vertebrae. Serum tartrate-resistant acid phosphatase 5b (TRAP-5b) and aminoterminal propeptide of collagen I (PINP) were analysed for resorption and osteocalcin (BGP) for bone formation. RESULTS: In both studies, ORX resulted in significant femoral and vertebral bone loss and microarchitectural deterioration after 5 months of ORX, and became more pronounced after 11 months. Biomechanical strength was also decreased. Serum levels for TRAP-5b and BGP increased while PINP levels were reduced or unchanged. Both daily and monthly IBN prevented or even restored ORX-induced changes in both studies, with the intermittent regimen showing a improvement in efficacy with respect to many of the biomechanical parameters.

Profile of patients who consult with internists for an osteoporosis assessment: The OSTEOMED registry.

BACKGROUND AND OBJECTIVES: Osteoporosis is considered a generalised skeletal disorder in which there is impaired bone resistance, which predisposes the individual to a greater risk of fracture. The aim of this cross-sectional study was to collect and present data on the main clinical characteristics of patients who consult medical internists in Spain. Understanding these characteristics can help in implementing action plans to improve these patients' care more effectively and efficiently. MATERIAL AND METHODS: Through an analysis of the Osteoporosis in Internal Medicine (OSTEOMED) registry, this study presents the main clinical characteristics of patients with osteoporosis who attended internal medicine consultations in 23 Spanish hospital centres between 2012 and 2017. We analysed the reasons for the consultations, the densitometric values, the presence of comorbidities, the prescribed treatment and other lifestyle-related factors. RESULTS: In total, 2024 patients with osteoporosis were assessed (89.87% women, 10.13% men). The patients' mean age was 64.1±12.1 years (women, 64.7±11.5 years; men, 61.2±14.2 years). There was no significant difference between the sexes in their history of recent falls (9.1% and 6.7%); however, there were significant differences in the daily intake of calcium from milk products (553.8±332.6mg for women vs. 450.2±303.3mg for men; p<.001) and in the secondary causes of osteoporosis (13% of men vs. 6.5% of women; p<.001). In the sample, there were 404 fractures (20%), with a notable number of confirmed vertebral fractures (17.2%, 35.6% in men vs. 15.2% in women; p<.001). A large portion of the patients did not undergo the indicated treatment and presented low levels of physical activity and sun exposure. A significant percentage of the patients presented associated comorbidities, the most common of which were hypertension (32%) and dyslipidaemia (28%). CONCLUSIONS: These results define the profile of patients with osteoporosis who attend internal medicine consultations in Spain. The results also show the multisystemic character of this condition, which, along with its high prevalence, determine that the specific internal medicine consultations dedicated to managing the condition are the appropriate place for caring for these patients.

Vertebral anti-fracture efficacy of strontium ranelate according to pre-treatment bone turnover.

UNLABELLED: Osteoporotic post-menopausal women patients in two randomised trials comparing the anti-fracture efficacy of strontium ranelate with placebo were separated into tertiles according to their baseline levels of biochemical markers of bone formation and resorption. The vertebral anti-fracture efficacy of strontium ranelate was shown to be independent of baseline bone turnover levels. INTRODUCTION: Bone turnover (BTO) levels vary among women at risk of osteoporotic fracture. Strontium ranelate is an anti-osteoporotic treatment increasing bone formation and reducing bone resorption. It was hypothesised that its anti-fracture efficacy would be independent of baseline BTO levels. METHODS: Post-menopausal women with osteoporosis from two pooled studies were stratified in tertiles according to baseline levels of two BTO markers: bone-specific alkaline phosphatase (b-ALP, n = 4995) and serum C-telopeptide cross-links (sCTX, n = 4891). Vertebral fracture risk was assessed over 3 years with strontium ranelate 2 g/day or placebo. RESULTS: In the placebo group, relative risk of vertebral fractures increased with BTO tertiles by 32% and 24% for patients in the highest tertile for b-ALP and CTX, respectively, compared to those in the lowest tertile. In the strontium ranelate group, incidences of vertebral fracture did not differ significantly across BTO tertiles. Significant reductions in vertebral fractures with strontium ranelate were seen in all tertiles of both markers, with relative risk reductions of 31% to 47% relative to placebo. Risk reduction did not differ among tertiles (b-ALP: p = 0.513; sCTX: p = 0.290). CONCLUSION: The vertebral anti-fracture efficacy of strontium ranelate was independent of baseline BTO levels. Strontium ranelate offers clinical benefits to women across a wide range of metabolic states.

The effectiveness of intermittent rat parathyroid hormone (1-34) treatment on low bone mass due to oestrogen or androgen depletion in skeletally mature rats.

Rat parathyroid hormone (PTH) 1-34 (4 microg/kg/day) was applied for 2.5 months to 9 month-old rats immediately after ovariectomy or orchidectomy or to 15 month-old rats with low bone mass which had been castrated 6 months before in order to know the effects on serum biochemistry parameters, lumbar and femoral bone mineral density, histology, cancellous and cortical bone histomorphometry, mineralisation content profile in cortical bone by backscattered-electron microscopy, and femoral torsion biomechanical testing. In ovariectomised rats, preventive PTH treatment avoided cancellous bone loss in tibial metaphysis and partially in lumbar vertebra, while in cortical bone, PTH increased endosteal resorption and periosteal formation. In intervention study, PTH did not restore cancellous bone but a strong endosteal and periosteal new bone formation was detected. In orchidectomised rats, PTH, in preventive study, avoided cancellous bone loss in metaphysis and lumbar vertebra, and a mild new bone formation in cortical bone was found. In intervention study, PTH maintained baseline cancellous bone mass, but in cortical bone a strong endosteal and periosteal new bone formation was detected. The PTH-induced new bone formation was confirmed by histology and by mineral content profiles. After castration, biomechanical properties were affected in females but not in male rats and PTH reverted this effect.

Effects of long-term strontium ranelate treatment on vertebral fracture risk in postmenopausal women with osteoporosis.

SUMMARY: Vertebral fractures are a major adverse consequence of osteoporosis. In a large placebo-controlled trial in postmenopausal women with osteoporosis, strontium ranelate reduced vertebral fracture risk by 33% over 4 years, confirming the role of strontium ranelate as an effective long-term treatment in osteoporosis. INTRODUCTION: Osteoporotic vertebral fractures are associated with increased mortality, morbidity, and loss of quality-of-life (QoL). Strontium ranelate (2 g/day) was shown to prevent bone loss, increase bone strength, and reduce vertebral and peripheral fractures. The preplanned aim of this study was to evaluate long-term efficacy and safety of strontium ranelate. METHODS: A total of 1,649 postmenopausal osteoporotic women were randomized to strontium ranelate or placebo for 4 years, followed by a 1-year treatment-switch period for half of the patients. Primary efficacy criterion was incidence of patients with new vertebral fractures over 4 years. Lumbar bone mineral density (BMD) and QoL were also evaluated. RESULTS: Over 4 years, risk of vertebral fracture was reduced by 33% with strontium ranelate (risk reduction = 0.67, p < 0.001). Among patients with two or more prevalent vertebral fractures, risk reduction was 36% (p < 0.001). QoL, assessed by the QUALIOST(R), was significantly better (p = 0.025), and patients without back pain were greater (p = 0.005) with strontium ranelate than placebo over 4 years. Lumbar BMD increased over 5 years in patients who continued with strontium ranelate, while it decreased in patients who switched to placebo. Emergent adverse events were similar between groups. CONCLUSION: In this 4- and 5-year study, strontium ranelate is an effective and safe treatment for long-term treatment of osteoporosis in postmenopausal women.

Bone disease induced by phenytoin therapy: clinical and experimental study.

Previous studies have made references to prolonged treatment with phenytoin as a possible risk factor in the development of osteoporosis and/or osteomalacia. We studied a group of 30 epileptic patients who were under long-term treatment with phenytoin (DPH) in an ambulatory regimen. We found the prevalence of osteoporosis to be 3.3% and of osteopenia to be 56.6%, affecting predominantly the femur, without any significant decrease in bone mineral density of the lumbar spine. These patients were showing signs of bone turnover uncoupling with increases in bone resorption markers. At this time, they also exhibited slight alterations in their phosphocalcium metabolism with trends to hypocalcemia and secondary hyperparathyroidism that was found not to be caused by a vitamin D deficiency as the serum levels of 25(OH)D and 1,25(OH)(2)D were normal. With the aims of corroborating these results and to investigate the physiopathological effects on the bone induced by anticonvulsant drugs we developed a further experimental study in which we administered DPH over a 6-week period with a dose of 5 g/kg/day to male Wistar rats that were in the growth phase. This treatment produced a decrease in overall BMD and bone mineral content in the femur. We did not find osteomalacia in the vertebral biopsy, but the administration of DPH to these animals decreased trabecular volume as well as lessened the thickness of osteoid edges together with an uncoupling in bone turnover. There was also a marked decrease in bone formation and a tendency towards increased bone resorption. We have also found a decrease in resistance to fracture by torsion in the biomechanical assay, which translates into an increase in bone fragility. In these male Wistar rats, the administration of DPH produced a tendency towards increasing the markers of resorption and, though changes in serum levels of calcium and phosphorus were not observed, to provoke an increase in the parathyroid hormone levels; with normal levels of 1,25(OH)(2)D which has produced the same inclination in rats as in humans.

Effect of risedronate on bone mass, remodelling and biomechanical strength in orchidectomized rats.

BACKGROUND: The ability of risedronate to prevent and/or treat orchidectomy-induced osteoporosis in male rats was studied. METHODS: Ninety-five 10-week-old male Wistar rats were sham-operated or orchidectomized. Prevention study: Sham: sham-operated rats; ORX: orchidectomized rats; ORX + RSD: orchidectomized rats, treated for 6 weeks with risedronate. Animals were sacrificed 6 weeks after surgery. Treatment study: Sham(1) and ORX(1): sham and orchidectomized rats sacrificed 3 months after orchidectomy; Sham(2), ORX(2) and ORX(2) + RSD: sham-operated, and orchidectomized rats treated with placebo or risedronate for 6 weeks starting 3 months after orchidectomy, and then sacrificed. Risedronate (0.5 mg/kg/day) and placebo (saline) were administered via oral gavage. After sacrifice, bone mineral density by DEXA, bone volume (BV/TV), osteocalcin (BGP), and serum carboxyterminal telopeptide of collagen type I (CTX) were measured. Femur low-rate torsion testing was performed. RESULTS: Orchidectomy produced an increase in bone remodelling with loss of BV/TV, without effects on torsional strength. Risedronate treatment partially prevented these effects. In the treatment study, risedronate reduced bone remodelling and restored BV/TV to levels higher than those of the sham group, improving biomechanical parameters. CONCLUSIONS: These results suggest that risedronate could be used as a prevention or treatment of male osteoporosis due to hypogonadism.

[Benign familial hyperphosphatasemia. A report of one case and diagnostic considerations]. / Hiperfosfatasemia familiar. Reporte de un caso y consideraciones diagnósticas.

Benign familial hyperphosphatasemia is a rare biochemical abnormality characterized by the presence of persistently elevated levels of serum alkaline phosphatase in several members of the same familiy, in the absence of disease or any known cause of hyperphosphatasemia. We describe one family affected with this biochemical abnormality and the epidemiology, genetic, isoenzymatic patterns and clinical significance of this entity are discussed.A 61-year-old man was referred to the Unit of Metabolic Bone Diseases for investigation of a lumbar pain with a history of urolithiasis and inguinofemoral hernia repair. The results of the physical examination and laboratory analysis were normal except for a high serum alkaline phosphatase level of 690 UI/l (reference range 40-129 UI/l). Isoenzymatic profile showed a 50% of intestinal variant, 33% of bone variant and 17% of liver variant isoenzymes. Skeletal radiographs and lumbar magnetic resonance imaging showed signs of osteoarthritis in the spine, bone scan showed a skeletal distribution of the radioisotope.One year later the biochemical exams showed similar raised levels of alkaline phosphatase. Family investigation revealed that one of the three sons of the patient had the same biochemical disorder.

Inhaled steroids do not decrease bone mineral density but increase risk of fractures: data from the GIUMO Study Group.

Although the negative effect of systemic steroids on bone is well documented, there is not clear evidence about possible adverse effects of inhaled steroids on bone metabolism and fractures. A cross-sectional study was performed on 105 women suffering from bronchial asthma treated with inhaled steroids and 133 controls. Bone mineral density (BMD) was measured by quantitative ultrasonography (QUS) at the calcaneus and by dual X-ray absorptiometry (DXA), at both the lumbar spine and proximal femur. Patients suffering from bronchial asthma showed no statistically significant changes in BMD as measured by DXA or QUS, compared with controls. A higher prevalence of fractures was found in the group of women with bronchial asthma, with an age-adjusted odds ratio of 2.79 (95% CI: 1.19-6.54). Inhaled steroids do not appear to decrease BMD, but are associated with an increased risk of fracture in women.

Postmenopausal women with colles' fracture have lower values of bone mineral density than controls as measured by quantitative ultrasound and densitometry.

Measurement of ultrasonographic parameters provides information concerning not only bone density but also bone architecture. We investigated the usefulness of ultrasonographic parameters and bone mineral density (BMD) to evaluate the probability of Colles' fracture. Two-hundred eighty-nine postmenopausal women (62.3 +/- 8.7 yr) with (n = 76) and without (n = 213) Colles' fracture were studied. BMD of lumbar spine and proximal femur was evaluated in all women by dual-energy X-ray absorptiometry (DXA) and speed of sound (SOS), broadband ultrasound attenuation (BUA), and stiffness in the calcaneus were measured by a Sahara ultrasonometer (Hologic). Patients suffering from Colles' fracture had lower values of BMD adjusted by height at the lumbar spine, L2-L4 (0.797 g/cm2 vs 0.860 g/cm2), femoral neck (0.685 g/cm2 vs 0.712 g/cm2 ), SOS (1518 m/sg vs 1525 m/sg), and stiffness (74.6 vs 77.7) (p < 0.05). Nevertheless, BUA values were similar in both groups. After stepwise logistic regression analysis, the area found under receiver operating characteristic (ROC) curves was 0.60 for L2L4 and 0.63 for a formula combining L2L4 and height. Our data suggest that patients suffering from Colles' fracture have lower values of BMD by DXA, SOS, and stiffness. However, the ability of these techniques to discriminate is low because the values for the area under ROC curve are 0.60 for L2-L4 and 0.63 for a formula derived of the combination of L2-L4 and height.

Postmenopausal women with Colles' fracture have bone mineral density values similar to those of controls when measured with calcaneus quantitative ultrasound.

BACKGROUND: It is a matter of controversy whether or not Colles' fracture is an osteoporotic fracture. Indeed, the usefulness of quantitative ultrasound in distinguishing Colles' fracture from normal fractures is also unclear. METHODS: A cross-sectional case-control study was done on 469 postmenopausal Spanish women, 121 with Colles' fracture and 348 controls. Assessment of risk factors for osteoporosis and measurement of calcaneus quantitative ultrasound were carried out using a Sahara, Hologic device. RESULTS: Patients with Colles' fracture had BUA, SOS, and QUI values that were similar to those of controls, and no statistically significant differences were found. We estimated ROC curves for SOS and a score based on a linear combination of height and SOS (SH-Score). The areas under both curves were 0.56 and 0.61, respectively, which was statistically significant. To obtain 5% false-negative and 10% false-positive figures, the T-score cut-off for SOS was -2.45 and -0.045, respectively. Of these, only 9.2% were classified as high risk and 11% as low risk with 79.8% undetermined. CONCLUSIONS: Patients with Colles' fracture had BUA, SOS, and QUI values that were similar to those of controls. Nevertheless, ROC curves calculated by a combination of height and SOS showed that quantitative calcaneus ultrasound may be a useful tool for identifying postmenopausal women with Colles' fracture. These results indicate that measuring bone mineral density with ultrasound only captures limited aspects of the pathophysiology of Colles' fractures.

Dual X-ray absorptiometry of the proximal femur: normal European values standardized with the European Spine Phantom.

Measurements of the proximal femur by dual X-ray absorptiometry (DXA) are assuming increasing importance in clinical and epidemiological studies. However, different DXA manufacturers have adopted varying approaches to measuring the femoral neck and trochanter regions with the result that there is as yet no agreement on normal ranges and how to cross-calibrate between different machines. In this Concerted Action (of the EU's 2nd Framework Programme), 12 clinical centers in eight countries recruited a total of 855 female and 517 male Caucasian subjects who were judged to be free of conditions known to cause secondary osteoporosis and who had not been treated with drugs known to affect bone mass. The DXA machines used were made by Hologic, Lunar, and Norland. Each machine was cross-calibrated with the European Spine Phantom prototype designed by Kalender. All femoral neck and trochanter results were expressed as standardized values and were first examined for possible bias due to between-brand differences in choice of areas for measurement. On average, trochanter areas were similar between brands but Norland chose a narrower neck region for analysis. Bone mineral density (BMA or BMD g/cm2) was log-normally distributed for all groups at the femoral neck but normally distributed at the trochanter in men and postmenopausal women. There were substantial between-center differences after cross-calibration in age-adjusted mean values at both sites and also in the rates of apparent bone loss with age and the amounts of scatter within populations about mean age-adjusted values. With the proviso that locally derived normal ranges would allow more accurate comparisons for clinical purposes, European normal ranges were derived for both neck and trochanter. Data obtained with the three individual brands of machine fitted these overall ranges well. Bone loss was apparent in premenopausal women at the femoral neck but not the trochanter. Postmenopausal women's data was somewhat better fitted by reference to years since menopause than to chronological age. This work provides a basis for conducting future epidemiological and clinical studies with more than one brand of machine as long as each individual subject, if measured consecutively, is measured on the same machine throughout.

Comparison of the efficacy and bioequivalence of two oral formulations of tiludronate in the treatment of Paget's disease of bone.

Tiludronate, an oral bisphosphonate used to treat Paget's disease of bone, is currently being studied as a treatment for osteoporosis. A multicenter, open-label, parallel-group study was performed to compare the efficacy of two tablet formulations of tiludronate in the treatment of Paget's disease. Eighty-eight patients with active Paget's disease were recruited. The diagnosis was based on radiologic evidence of bone lesions, and all patients included in the study had serum alkaline phosphatase (SAP) levels equal to or more than twice the upper normal value of the local laboratory that assayed the sample. Each patient received treatment with oral tiludronate 400 mg/d for 84 +/- 2 days; 39 patients received the previously tested tablet formulation 3C1, and 49 patients received formulation 9O1, which is prepared using an improved manufacturing technique. The objective of this study was to determine whether the two formulations have an equivalent therapeutic effect, the primary end point being SAP levels in both groups after 3 months of treatment. This equivalence is commonly assessed by comparing pharmacokinetic data; however, in previous studies of tiludronate, large intra-individual variability prevented statistically valid comparisons of the data. Therefore, in addition to pharmacokinetic data, biochemical and clinical response data were collected during the trial. The secondary objectives of the trial were to measure the plasma levels and to assess the efficacy and safety of the two tiludronate formulations. The relative pharmacologic activities of the two formulations were assessed by comparison of the confidence intervals of levels of SAP at monthly intervals. After 3 months of treatment, the 90% confidence interval of the difference between the formulations was included in the reference confidence interval. These findings suggest that the 9O1 and 3C1 formulations did not show a significant difference in therapeutic activity. Furthermore, after 3 months of treatment, the frequency of normalization of SAP levels was 30.6% in the 9O1 treatment group and 28.2% in the 3C1 treatment group. The percentage of patients responding to treatment (defined as a decrease in SAP levels of at least 50% from baseline) was 67.3% in the 9O1 treatment group and 69.2% in the 3C1 treatment group. Statistical analyses performed on the maximum and minimum plasma concentrations of tiludronate showed no significant differences between the two formulations. In this trial, the two tablet formulations of tiludronate demonstrated therapeutic and pharmacokinetic equivalence.

Bone mass assessment in rats by dual energy X-ray absorptiometry.

At present there are many techniques available for determining bone mass, measurement of which is essential for monitoring osteopenia. Rats are preferred to other laboratory species when designing animal studies on osteoporosis. The precision and accuracy of dual energy X-ray absorptiometry (DXA) for the assessment of bone mineral density (BMD) and bone mineral content (BMC) in laboratory animals were assessed. Precision, expressed as a coefficient of variation (CV), was measured, making five determinations (Hologic QDR-1000) on lumbar spine (in vivo) and femur (in vitro), both with and without repositioning. The correlation (r) between densitometric parameters and mineral content of bone ashes was calculated both in lumbar spine (in vivo) and in femur (in vitro). In our study, DXA had good precision, better in femur (CV 0.53%) than in lumbar spine (L2-L4) (CV 1.0%). Repositioning did not increase significantly the coefficients of variation (CV 0.61% and 1.2%, respectively). The linear regression between BMD and ash weight, calcium and phosphorous content showed high correlation coefficients (r = 0.64-0.85, p < 0.05). Although we found an overestimate of values of BMC with respect to ash weight (21% in lumbar spine and 31% in femur), the correlation between BMC and mineral content was high (r = 0.96-0.99, p < 0.05). The results suggest that the DXA technique has the precision necessary when used to assess BMD and BMC in small laboratory animals.