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Objective: To explore the genetic causal association between osteoporosis (OP) and iron status through Mendelian randomization (MR)., Methods: Publicly available genome-wide association study (GWAS) summary data were used for MR analysis with four iron status-related indicators (ferritin, iron, total iron binding capacity, and transferrin saturation) as exposures and three different types of OP (OP, OP with pathological fracture, and postmenopausal OP with pathological fracture) as outcomes. The inverse-variance weighted (IVW) method was used to analyze the genetic causal association between the four indicators of iron status and OP. The heterogeneity of MR results was determined using IVW and MR-Egger methods. The pleiotropy of MR results was determined using MR-Egger regression. A leave-one-SNP-out test was performed to determine whether the MR results were affected by a single nucleotide polymorphism (SNP). The weighted median method was conducted to further validate our results., Results: Based on IVW, MR-Egger and weighted median models, we found no causal association between iron status (ferritin, iron, total iron binding capacity, or transferrin saturation) and OP (P beta > 0.05 in all models). IVW and MR-Egger analysis of OP with pathological fracture and iron status indicators showed no potential genetic causal association (P beta > 0.05 in the two analyses). The results of the weighted median were consistent with those of IVW (P beta > 0.05 in all analyses). There was no potential genetic causal association between iron status and postmenopausal OP with pathological fracture based on serum iron (P beta >0.05 in all models). No heterogeneity or horizontal pleiotropy was found in any of the analyses. None of the leave-one-out tests in the analyses found any SNP that could affect the results of MR., Conclusion: Our results demonstrate that there is no genetic causal association between OP and iron status, but the effects of other factors were not excluded., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xu, Ma, Chen, Zhang, Zheng, Si, Wu, Liu, Li, Wu and Shen.)

Introduction: Osteoblasts require substantial amounts of energy to synthesize the bone matrix and coordinate skeleton mineralization. This study analyzed the effects of mitochondrial dysfunction on bone formation, nano-organization of collagen and apatite, and the resultant mechanical function in mouse limbs., Materials and Methods: Limb mesenchyme-specific Tfam knockout (Tfam f/f ;Prx1-Cre: Tfam-cKO) mice were analyzed morphologically and histologically, and gene expressions in the limb bones were assessed by in situ hybridization, qPCR, and RNA sequencing (RNA-seq). Moreover, we analyzed the mitochondrial function of osteoblasts in Tfam-cKO mice using mitochondrial membrane potential assay and transmission electron microscopy (TEM). We investigated the pathogenesis of spontaneous bone fractures using immunohistochemical analysis, TEM, birefringence analyzer, microbeam X-ray diffractometer and nanoindentation., Results: Forelimbs in Tfam-cKO mice were significantly shortened from birth, and spontaneous fractures occurred after birth, resulting in severe limb deformities. Histological and RNA-seq analyses showed that bone hypoplasia with a decrease in matrix mineralization was apparent, and the expression of type I collagen and osteocalcin was decreased in osteoblasts of Tfam-cKO mice, although Runx2 expression was unchanged. Decreased type I collagen deposition and mineralization in the matrix of limb bones in Tfam-cKO mice were associated with marked mitochondrial dysfunction. Tfam-cKO mice bone showed a significantly lower Young's modulus and hardness due to poor apatite orientation which is resulted from decreased osteocalcin expression., Conclusion: Mice with limb mesenchyme-specific Tfam deletions exhibited spontaneous limb bone fractures, resulting in severe limb deformities. Bone fragility was caused by poor apatite orientation owing to impaired osteoblast differentiation and maturation., (© 2022. The Japanese Society Bone and Mineral Research.)

Many natural structures use a foam core and solid outer shell to achieve high strength and stiffness with relatively small amounts of mass. Biological foams, however, must also resist crack growth. The process of crack propagation within the struts of a foam is not well understood and is complicated by the foam microstructure. We demonstrate that in cancellous bone, the foam-like component of whole bones, damage propagation during cyclic loading is dictated not by local tissue stresses but by heterogeneity of material properties associated with increased ductility of strut surfaces. The increase in surface ductility is unexpected because it is the opposite pattern generated by surface treatments to increase fatigue life in man-made materials, which often result in reduced surface ductility. We show that the more ductile surfaces of cancellous bone are a result of reduced accumulation of advanced glycation end products compared with the strut interior. Damage is therefore likely to accumulate in strut centers making cancellous bone more tolerant of stress concentrations at strut surfaces. Hence, the structure is able to recover more deformation after failure and return to a closer approximation of its original shape. Increased recovery of deformation is a passive mechanism seen in biology for setting a broken bone that allows for a better approximation of initial shape during healing processes and is likely the most important mechanical function. Our findings suggest a previously unidentified biomimetic design strategy in which tissue level material heterogeneity in foams can be used to improve deformation recovery after failure.

Aim of the study is to determine the possible roles of p53, cyclin D1, β-catenin and Ki-67 in the increase in risk of fractures in patients with giant cell tumor of bone. The study included a total of 164 patients with giant cell tumor of bone (GCTB), 21 (12.8%) with and 143 (87.2%) without fracture. The samples were analyzed immunohistochemically for expression of Ki-67, p53, cyclin D1 and β-catenin. According to the immunohistochemical expression of p53 and Ki 67 in mononuclear stromal cells, as well as of cyclin D1 in multinuclear giant cells, there was no significant association with immunopositivity and risk of fractures. However, our research revealed that patients with cytoplasmic expression of b-catenin in stromal cells had three times more frequent occurrence of pathological fractures, which was highly statistically significant (χ2 = 7.065; p = 0.008). Moreover, a highly statistically significant correlation between the nuclear expression of β-catenin in giant cells and the incidence of pathological fractures was also found (χ2 = 8.824; p = 0.003). The study showed that β-catenin expression highly correlates with the incidence of pathological fractures in patients with GCTB. Taking into account that β-catenin is closely linked to activation of the Wnt signaling pathway in GCTB pathogenesis, one could postulate that activation of the Wnt pathway is one of the contributing factors to locally destructive behavior of this tumor, as well as to the incidence of pathological fractures.

The case of a recurrent phosphaturic mesenchymal tumour of the maxillary sinus 10 years after the first surgical excision is reported. The neoplasm first presented with paraneoplastic osteomalacia causing a pathological femur fracture. A right maxillary sinus tumour was identified and treated thereafter. The patient had no local symptoms and serum electrolytes returned to normal after surgical removal of the tumour. However, 10 years later, the patient's urine Ca and P levels increased and an octreoscan detected a new tumour in the right maxillary sinus. Early diagnosis prevented the effects of the paraneoplastic activity of the neoplasm. This case emphasises the importance of specific, close follow-up, because the neoplasm rarely produces local signs indicating its position. To our knowledge, this is the first reported case of a late relapse presenting without relevant symptoms (local pain or swelling or pathological fractures)., (2014 BMJ Publishing Group Ltd.)

Context: Polygonum amplexicaule D. Don var. sinense Forb. (Polygonaceae) (PAF) is a well known traditional herb used to treat some diseases, such as fractures, rheumatoid arthritis, muscle injury, and pain. However, its pharmacological mechanism of promoting the healing of fractures is still unknown., Objective: The present study was designed to investigate the effects of PAF ethanol extracts on the proliferation and differentiation of osteoblastic MC3T3-E1 cell in vitro, thereby to illuminate the pharmacological mechanism to promote the healing of fractures., Materials and Methods: The effects of PAF ethanol extracts on MC3T3-E1 cell proliferation and differentiation were detected by using CCK-8, cell cycle, alkaline phosphatase (ALP), and prostaglandin E(2) (PGE(2)) assays in vitro., Results: The results showed that PAF ethanol extracts significantly stimulated cell proliferation at 0.1-100 μg/mL and the proportion of cells in S-phase increased from 16.33 to 27.29% in osteoblastic MC3T3-E1 cells. Moreover, PAF ethanol extracts increased ALP expression in MC3T3-E1 cells at the concentration from 0.1 to 100 μg/mL and inhibited PGE(2) production induced by TNF-α in osteoblasts at the concentrations ranging from 10 to 100 μg/mL in MC3T3-E1 osteoblasts., Discussion and Conclusion: These results indicated that PAF directly stimulates cell proliferation and differentiation of osteoblasts; therefore, this study preliminarily explored the pharmacological mechanism of PAF to promote the healing of bone rheumatism and various fractures.

To address the cause of fragility fractures, an understanding of the determinants of bone strength is needed. Identifying patients at increased fracture risk should take into account bone quantity, quality, and turnover. Postmenopausal osteoporosis remains the most common derangement of bone strength; however, decreased bone strength can also result from secondary causes of osteoporosis. In order to properly manage patients with fragility fractures, assessment should include a focused medical history and physical examination, proper laboratory investigation, dual-energy x-ray absorptiometry screening, and, if necessary, use of the fracture risk assessment tool (FRAX). Treatment options will include nonpharmacologic treatment such as calcium and vitamin D and pharmacologic treatment with antiresorptive or anabolic agents to prevent future fractures. Bisphosphonates remain the standard treatment for osteoporosis. Concerns of oversuppression of bone turnover on long-term bisphosphonate treatment can be addressed with a drug holiday depending on the patient's fracture risk. An anabolic agent such as teriparatide is a powerful tool for the prevention of fragility fractures and should be reserved for patients at high risk for fracture, such as those with declining bone mineral density despite bisphosphonate treatment. Careful evaluation of all patients with a fragility fracture will enable the orthopaedic surgeon to identify the cause of fracture and implement a treatment plan that can prevent subsequent fractures in this vulnerable population.

Periprosthetic fractures of the distal femur most commonly present as fragility fractures associated with relatively minor trauma. These injuries are often complicated by osteopenia of the distal femur secondary to stress shielding or osteolysis. Effective management of periprosthetic fractures of the distal femur requires knowledge of both fracture fixation techniques and revision arthroplasty. This article reviews the treatment options for these challenging fractures with a particular focus on the management of displaced fractures with a stable prosthesis.

Unlabelled: Young mice over-expressing Runx2 fail to gain bone relative to wild type mice with growth and present spontaneous fractures. It allows, for the first time in rodents, direct assessment of anti-fracture efficacy of strontium ranelate which was able to decrease caudal vertebrae fracture incidence through an improvement of trabecular and cortical architecture., Introduction: The aim was to investigate whether strontium ranelate was able to decrease fracture incidence in mice over-expressing Runx2, model of severe developmental osteopenia associated with spontaneous vertebral fractures., Methods: Transgenic mice and their wild type littermates were treated by oral route with strontium ranelate or vehicle for 9 weeks. Caudal fracture incidence was assessed by repeated X-rays, resistance to compressive loading by biochemical tests, and bone microarchitecture by histomorphometry., Results: Transgenic mice receiving strontium ranelate had significantly fewer new fractures occurring during the 9 weeks of the study (-60%, p < 0.05). In lumbar vertebrae, strontium ranelate improves resistance to compressive loading (higher ultimate force to failure, +120%, p < 0.05) and trabecular microarchitecture (higher bone volume and trabecular number, lower trabecular separation, +60%, +50%, -39%, p < 0.05) as well as cortical thickness (+17%, p < 0.05). In tibiae, marrow cavity cross-section area and equivalent diameter were lower (-39%, -21%, p < 0.05). The strontium level in plasma and bone was in the same range as the values measured in treated postmenopausal women., Conclusions: This model allows, for the first time, direct assessment of anti-fracture efficacy of strontium ranelate treatment in rodents. In these transgenic mice, strontium ranelate was able to decrease caudal vertebral fracture incidence through an improvement of trabecular and cortical architecture.

Objectives: To evaluate the health implications and economic burden on society of osteoporotic fractures as a major source of morbidity and mortality in the ageing population., Methods: We have summarised the findings of a literature review of French studies published between 1960 and 2009, characterised the epidemiology of osteoporosis and osteoporotic fractures, and predicted future trends., Results: Published data for France supported the observation that osteoporosis is under-diagnosed in many countries. The incidence of fracture increased exponentially with age, alongside a concurrent decrease in bone mineral density, a risk factor for fracture. Combined with a projected rise in the French elderly population, this poses a significant burden for the future. The incidence of fracture was high in the osteopenic population; consequently, fragility fractures may be underestimated if reports focus on osteoporotic women only. As in many other countries, French data revealed that women have a higher incidence of osteoporotic fractures than men, although mortality from hip fracture was higher in men., Discussion: Due to ageing of the population, an increase in the number of people suffering from fractures is predicted over the next few decades unless preventative action is taken, highlighting the need for improved diagnosis and screening in postmenopausal women., (Copyright © 2010 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.)

The life expectancy of individuals infected with HIV has improved greatly since the institution of combination antiretroviral therapy. However, many metabolic derangements have been discovered with long-term combination antiretroviral treatment, including lipodystrophy; insulin resistance; and, more recently, abnormal bone metabolism. It is well-documented that bone mineral density (BMD) in HIV-positive patients is lower compared with the expected BMD in non-HIV-positive patients. The underlying cause of lower BMD is unknown but is thought to be a multifactorial process. Conflicting evidence exists regarding the effect of antiretroviral exposure and duration of treatment, antiretroviral type, and cumulative HIV viral exposure on bone health. Here we review the bone changes that occur with HIV infection and treatment.

Patients with cancers such as breast or prostate cancer who have been treated with hormone deprivation therapies or anti-cancer agents for certain periods of time frequently manifest reduced bone mass or pathological fractures during their clinical course. These are likely due to an imbalance between osteoblastic bone formation and osteoclastic bone resorption resulting from hypogonadism. Bone should be carefully monitored in cancer patients who are going to continually receive adjuvant hormonal or anti-cancer therapies. Administration of anti-bone resorption agents such as bisphosphonates may be necessary to maintain bone mineral density and protect pathological fractures in these cancer patients.

The central role of bone morphogenetic proteins (BMPs) in the remodelling process of the human skeleton has been identified in numerous experimental and clinical studies. BMPs appear to be key agents in the osteoblastic differentiation of mesenchymal stem cells, and more recent evidence implicates them with the cells of the osteoclastic lineage. BMP-2, BMP-4, BMP-6 and BMP-7 have been studied in the context of osteoporosis and have been associated with its pathophysiological pathways. The theoretical advantages of local or systemic treatment of osteoporotic fractures with BMPs include the potential of inducing a rapid increase in bone strength locally at the fractured area and systemically in the entire skeleton, as well as accelerating the bone-healing period. Animal models of osteoporotic fractures suggested that the induction of new bone by local or systemic use of BMP-7 should be investigated as potential bone augmentation therapy to improve bone quality in symptomatic spinal osteoporosis. As our knowledge expands, new innovations may provide clinicians with advanced biologically-based therapies for the successful treatment of osteoporotic fractures., (Copyright 2009 Elsevier Ltd. All rights reserved.)

Objective: African Americans with rheumatoid arthritis (RA) may be at increased fracture risk. We applied the World Health Organization (WHO) Fracture Risk Assessment Tool (FRAX) and National Osteoporosis Foundation (NOF) guidelines to a cohort of African Americans with early RA to identify which patients were recommended for osteoporosis treatment., Methods: Risk factors and bone mineral density (BMD) were assessed in a cohort of African Americans with RA. The WHO FRAX tool estimated 10-year fracture risk. Patients were risk stratified using FRAX without BMD to identify which individuals might be most efficiently targeted for BMD testing., Results: Participants (n = 324) had a mean age of 51 years and included 81% women. There were no associations of RA disease characteristics with BMD. The proportion of patients recommended for osteoporosis treatment varied from 3-86%, depending on age and body mass index (BMI). Ten-year fracture risk calculated with BMI only was generally the same or higher than fracture risk calculated with BMD; adding BMD data provided the most incremental value to risk assessment in patients 55-69 years of age with low/normal BMI, and in those > or =70 years of age with BMI > or =30 kg/m2., Conclusion: A high proportion of African Americans with RA were recommended for treatment under the 2008 NOF guidelines. FRAX without BMD identified low-risk patients accurately. Systematic application of FRAX to screen high-risk groups such as patients with RA may be used to target individuals for BMD testing and reduce the use of unnecessary tests and treatments.

Osteoporosis is a bone disease leading to an increased fracture risk. It is considered a complex multifactorial genetic disorder with interaction of environmental and genetic factors. As a candidate gene for osteoporosis, we studied vitamin D binding protein (DBP, or group-specific component, Gc), which binds to and transports vitamin D to target tissues to maintain calcium homeostasis through the vitamin D endocrine system. DBP can also be converted to DBP-macrophage activating factor (DBP-MAF), which mediates bone resorption by directly activating osteoclasts. We summarized the genetic linkage structure of the DBP gene. We genotyped two single-nucleotide polymorphisms (SNPs, rs7041 = Glu416Asp and rs4588 = Thr420Lys) in 6,181 elderly Caucasians and investigated interactions of the DBP genotype with vitamin D receptor (VDR) genotype and dietary calcium intake in relation to fracture risk. Haplotypes of the DBP SNPs correspond to protein variations referred to as Gc1s (haplotype 1), Gc2 (haplotype 2), and Gc1f (haplotype3). In a subgroup of 1,312 subjects, DBP genotype was found to be associated with increased and decreased serum 25-(OH)D(3) for haplotype 1 (P = 3 x 10(-4)) and haplotype 2 (P = 3 x 10(-6)), respectively. Similar associations were observed for 1,25-(OH)(2)D(3). The DBP genotype was not significantly associated with fracture risk in the entire study population. Yet, we observed interaction between DBP and VDR haplotypes in determining fracture risk. In the DBP haplotype 1-carrier group, subjects of homozygous VDR block 5-haplotype 1 had 33% increased fracture risk compared to noncarriers (P = 0.005). In a subgroup with dietary calcium intake <1.09 g/day, the hazard ratio (95% confidence interval) for fracture risk of DBP hap1-homozygote versus noncarrier was 1.47 (1.06-2.05). All associations were independent of age and gender. Our study demonstrated that the genetic effect of the DBP gene on fracture risk appears only in combination with other genetic and environmental risk factors for bone metabolism.

Unlabelled: Time-dependent changes in bone markers in delayed or nonunion of vertebral fracture were compared with those of normal union. Thirty-three patients with a fresh vertebral fracture were enrolled. Urinary Type I collagen C-terminal telopeptide, pyridinoline, deoxypyridinoline, serum C-terminal telopeptide, and N-midportion of osteocalcin (OC(N-mid)) were determined at the time of hospital admission (within 24 hours after the fracture event in all cases) and at 2, 4, 12, 24, and 48 weeks thereafter. Subjects were divided into two groups according to the results of MR images taken 48 weeks after fracture. Twenty-four were normally united (Group N) and nine had delayed or nonunion (Group D) of the spine. No differences between values of bone resorption markers in Group N and Group D were observed at any time. Serum OC(N-mid) in Group N started to increase at 2 weeks and reached the peak value at 24 weeks (180%); however, serum OC(N-mid) in Group D increased at most 120% from baseline to 4 weeks. Values of serum OC(N-mid) in Group N were higher at 24 and 48 weeks than those in Group D. Impairment of fracture healing was strongly associated with a deficit in the increase of osteocalcin in the later stage of fracture repair., Level of Evidence: Level II, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence.

Chronic renal insufficiency (CRI) causes important modifications in the metabolism of phosphorus and calcium, to which frequently resulting in serious disorders of the skeleton, including demineralization, reduction of the bone resistance and a higher risk of fractures. Renal osteodystrophy is the term used to describe these disorders; they are generally heterogeneous and are classified according to the state of bone turnover into secondary hyperparathyroidism, adynamic bone, and osteomalacia. The incidence of hip fractures in the patients with CRI is higher than in the general population. Hip fractures are an important cause of morbidity and mortality. The evaluation of the fracture risk in the patients with different degrees of CRI is problematic, in particular because of the difficulty in identifying fractures, especially vertebral ones. The instrumental index that best expresses the fracture risk in the general population is bone mineral density (BMD); however, the relationship between low BMD and CRI is disputed. Bone disorders in patients with CRI have in fact a multifactorial pathogenesis and low BMD is not the only risk factor for fractures. Besides densitometric evaluation, also that vertebral morphometric evaluation would be desirable in patients with CRI. The fracture risk increases progressively with the severity of chronic renal disease and it is especially high in patients with renal insufficiency in more advanced-stages CRI (creatinine clearance<15-20 mL/min). However, not only in patients with severe CRI undergoing dialysis, but also in those with milder renal disease is the risk of bone fractures high.

Background: The serum concentration of cross-linked telopeptide of type I collagen (ICTP) has been reported to be a useful marker and for both diagnosis and monitoring of bone metastasis. This study was performed to clarify the changes in various bone turnover markers, including ICTP, after bone fragility fracture., Methods: Seventy-six bone fragility fracture patients (14 men and 62 postmenopausal women; mean age, 77.0 years) were evaluated for bone resorption markers, including serum ICTP. We measured urinary N-terminal telopeptides of type I collagen (NTX) several times after fracture. Furthermore, serum ICTP, serum NTX, urinary deoxypyridinoline (DPD), and urinary C-telopeptide-cross-linked type I collagen (CTX) were measured at the times of both minimum and maximum urinary NTX., Results: Urinary NTX was increased significantly from 86.4 +/- 57.9 to 214.3 +/- 137.2 nmol BCE/mmol Cr following fracture. Serum ICTP showed a similar significant increase from 7.6 +/- 4.7 to 10.4 +/- 5.5 ng/ml in bone fragility fracture patients. Furthermore, other markers also showed similar increases. The level of increase in urinary NTX (148.0%) was especially high compared with other bone resorption markers. On the other hand, the level of increase in serum ICTP (36.8%) was similar to that in serum NTX (39.8%). Serum ICTP levels were significantly correlated with other bone resorption markers, with an especially strong correlation between serum ICTP and serum NTX (r = 0.647, P < 0.001). The percentage of cases in which ICTP exceeded the cutoff value for suspected bone metastasis in postmenopausal women was 73.6%., Conclusions: The value of ICTP increases with bone fragility fracture and is correlated with other bone resorption markers, and ICTP obviously exceeded the reference value as compared with other bone resorption markers.

Context: Osteoporosis has a significant genetic component. The aromatase-dependent conversion of androgenic precursors is the main source of estrogens in postmenopausal women., Objective: The objective of the investigation was to study the relationship of a set of single nucleotide polymorphisms (SNPs) of the aromatase gene with osteoporosis and determine their functional influence on gene transcription., Design, Participants, and Methods: This was a case-control study including 135 women with vertebral fractures due to postmenopausal osteoporosis and 312 controls. Alleles at four SNPs situated between exons I.2 and 3 were determined by Taqman assays. Total aromatase RNA and differential allelic-specific expression were studied by RT-real time PCR in adipose tissue samples taken from 50 individuals., Results: The SNPs studied were in strong linkage disequilibrium. A common haplotype, present in about half of the population, was identified as being associated with an increased risk of fractures (odds ratio 1.8, 95% confidence interval 1.2-2.8, P = 0.006). There was evidence of differential allelic expression. In heterozygous individuals, transcripts bearing T alleles at rs700518 SNP (which were included in the risk haplotype) were less abundant than those with the alternative C alleles (P < 0.001). Total aromatase expression was four times lower in fat samples from individuals who were homozygotes for the unfavorable alleles than in the opposite homozygotes (P = 0.007)., Conclusions: A common haplotype of aromatase associated with gene expression is also associated with the risk of osteoporotic vertebral fractures in postmenopausal women. These data are in line with the hypothesis that the aromatase-dependent synthesis of estrogens plays an important role in bone homeostasis in postmenopausal women.

Statins were developed for the treatment of lipid disorders and have been proved to reduce cardiovascular morbidity and mortality when used for primary or secondary prevention. Beneficial effects in patients with osteoporotic fractures or rheumatoid arthritis (RA) have been suggested but remain unproven. Cardiovascular morbidity and mortality are increased in patients with RA or systemic lupus erythematosus, who should undergo serum lipid assays. When these show dyslipidemia, statin therapy should be started according to current recommendations.

The ability to assess a patient's risk of fracture is fundamental to the clinical role of bone densitometry. Fracture discrimination is quantified by the relative risk (RR), defined as the increased risk of fracture for a 1 standard deviation decrease in bone mineral density (BMD). The larger the value of RR, the more effective measurements are at identifying patients at risk of fracture. Epidemiological studies show that RR values for predicting the risk of any fracture are approximately the same for all BMD measurement sites. In this study, we show theoretically that this interesting observation is predictable and a consequence of two related observations: (1) that fracture prediction by BMD measurement sites distant from the fracture site is quantitatively explained by the correlation of BMD measurements and (2) that all correlation coefficients between distant BMD sites are comparable, with values in the range r = 0.55-0.65. The first of these conditions (referred to as the correlation hypothesis) is important because it sets a lower limit on the RR values at distant BMD sites on the assumption that measurements at these sites contain no independent information about fracture risk over and above that provided by their correlation with the fracture site BMD. If the correlation hypothesis is true, the present study points to the importance of the correlation coefficient between BMD sites as a key index that is indicative of the ability of different types of measurement to predict fracture risk. If, on the contrary, the correlation hypothesis is not valid, there is scope to improve bone densitometry by further studies to better identify those measurements that do provide independent information about fracture risk and how best to integrate this information with existing techniques to improve decision making.

The aim of this study was to determine whether the probability of osteoporosis and osteopenia was affected by the risk factors, physical examination findings, or radiological investigations such as spinal X-rays in postmenopausal women. We assessed risk factors such as use of hormone replacement therapy, physical activity level, calcium intake, smoking, caffeine consumption, long-term immobilization, previous history of fracture, family history of fracture, presence of certain systemic diseases (hyperthyroidism or hyperparathyroidism), or use of medications (corticosteroids or others), physical examinations, and presence of vertebral fractures on spinal X-rays. Patients' bone mineral density (BMD) was evaluated using dual energy X-ray absorptiometry (DXA) in the lumbar spine, and we compared the risk factors between osteopenic and osteoporotic women according to DXA. We evaluated 235 postmenopausal women who attended our osteoporosis outpatient clinic. Those patients were divided into two groups as either osteopenic (n = 67, mean age: 63.1 years) or osteoporotic (n = 168, mean age: 66.2 years) according to WHO criteria. The lumbar spinal (L1-L2) T-score values were -1.5 +/- 0.6 and -3.1 +/- 0.6 in osteopenic and osteoporotic groups, respectively. There were significant differences between the two groups in terms of mean age and lumbar BMD (p = 0.009 and p < 0.001, respectively). We also observed that vertebral tenderness on palpation, back pain, and existing vertebral fracture (fx) were significantly different between the osteopenic and osteoporotic groups (p < 0.05). As a result of the statistical analysis, we found an equation to determine osteopenic and osteoporotic women by using those four factors (age, vertebral tenderness on palpation, back pain, and existing vertebral fx) in multivariate stepwise logistic regression. The equation is as follows: Y (DXA) = -2.9024 + 0.044 (age in year) + 0.819 (vertebral fx) + 0.877 (pain) + 1.136 (vertebral tenderness). We can estimate whether a postmenopausal woman is osteopenic or osteoporotic based on these risk factors by using the stepwise logistic regression equation.

Purpose of Review: The bisphosphonates alendronate and risedronate, given orally once weekly, are the cornerstone of treatment of postmenopausal osteoporosis, as well as of male and secondary osteoporosis. They reduce significantly the risk of vertebral and nonvertebral fractures; their effects appear early, within 6-12 months, and appear to be sustained. Several questions remain unanswered, however. In addition, data on a new bisphosphonate became available in 2004., Recent Findings: The optimal duration of treatment has not been clearly established. Long-term data with alendronate are now available, indicating a persistence of alendronate effects on bone mineral density and bone turnover markers several years after stopping treatment given for 5 years. Whether these effects translate into sustained reduction of fractures needs to be further analyzed. Because of their efficacy, bisphosphonate use has been explored in other forms of osteoporosis, such as after androgen deprivation therapy for prostatic cancer. The challenge of long-term compliance with treatment of osteoporosis has triggered the use of intermittent bisphosphonate. The effects of intermittent oral and intravenous ibandronate on bone mineral density, bone turnover, and fractures have been recently reported., Summary: The mechanism by which bisphosphonates improve bone strength is not yet fully understood but probably involves complex effects on different components of bone strength, such as microarchitecture.

It is widely believed that the most reliable BMD measurement for predicting fracture risk at any given skeletal site is one made at the fracture site itself. This study examines the hypothesis that the ability of BMD measurements at other distant sites in the skeleton remote from the fracture site to predict fracture risk is due to their correlation with the BMD measurements at the fracture site. We refer to this assumption as the correlation hypothesis. We show that the correlation hypothesis predicts the relationship betadist = rbetafrac, where beta is the gradient of the exponential relationship between fracture risk and Z-score, betafrac is the beta-value for the fracture site, betadist the beta-value for the distant BMD site, and r is the correlation coefficient between the Z-scores at the two sites. In practice it is important to consider the effect of BMD measurement errors on the (r, beta) relationship. We show that the effect of errors at the distant site is to reduce betadist and r in a way that preserves their original relationship. When errors at the fracture site are taken into account the effect on the (r, beta) plot is for the point representing the fracture site to fall below the extrapolation of the straight-line relationship predicted for the points representing the distant BMD sites. We tested the correlation hypothesis by using data from the Study of Osteoporotic Fractures to examine the (r, beta) plots for hip, spine and forearm fractures. For the hip the data are consistent with a straight-line relationship and suggest that measurements made at other sites provide no additional information about fracture risk over and above that provided by hip BMD itself. For spine and forearm fractures the data show that distant sites do provide additional information about fracture risk in a way that is quantitatively consistent with the BMD measurement errors reported in cadaver studies. It is clear that random BMD errors at the fracture site cause loss of information about fracture risk and that some of this lost information is recoverable from measurements made at other sites in the skeleton. Overall, this study points to BMD correlation as an important factor in explaining the ability of measurements made at distant sites to predict fracture risk.

Introduction: The aim of this study was to point out some dilemmas about the existence and pathogenesis of primary diabetic osteopathy as a separate entity, based on currently available studies. Expert disagreements are present not only about the occurrence of generalized osteopathy with diabetic disease, but also about direct relationship between metabolic diabetes control and bone metabolism and influence of disease duration and sex on bone changes., Pathogenesis of Diabetic Osteopathy: Decreased bone formation is the basic mechanism leading to decreased bone mass. Biochemical markers showed no clear connection with bone density measurement. Insulin and insulin-like growth facotr (IGF) affect bone metabolism. OSTEOPATHY IN PATIENTS WITH DIABETIC DISEASE-TYPE1: Some clinical studies have shown that patients with diabetic disease-type have a mild decrease in bone mass, while others have not presented such results. OSTEOPATHY IN PATIENTS WITH DIABETIC DISEASE-TYPE2: In patients with diabetic disease-type 2 the risk for osteopathy is even less defined. Patients treated with oral hypoglycemics present with higher decrease of bone mass has than patients treated with insulin therapy. This could partly be explained by anabolic effects of insulin on bones., Bone Fractures in Patients With Diabetic Disease: Literature data are contradictory concerning the occurrence of bone fractures in diabetic patients. A survey of bone fracture occurrence in diabetic patients was performed in "Veljko Vlahović Medical Center" in Vrbas and it included a group of 100 patients with diabetic disease. The results show that 12 patients had some fractures: mostly females in postmenopause, aged and with secondary insulin-dependent diabetes and most frequently arm fractures. Considering contradictory literature data, further longitudinal studies are necessary.

To compare the ability of the bone mineral density (BMD) at the distal forearm, collagen I alpha 1 (COLIA1) polymorphism, and ultrasound stiffness to identify individuals with increased risk of wrist fracture, we studied 183 postmenopausal Czech women with a wrist fracture and 178 postmenopausal controls, ages 45-70 years. The genotypes "Ss" and "ss" were significantly overrepresented among fracture cases. The BMD measurements at the femoral neck, total femur, and distal forearm as well as ultrasound stiffness of the heel, broadband ultrasound attenuation (BUA), and speed of sound (SOS) were significantly lower in the fracture cohort. BMD of the distal forearm was the main determinant of susceptibility to the wrist fracture. Weight, the COLIA1 genotype, and ultrasound SOS further strengthened the predictive value of BMD. However, we found interaction between weight and both the COLIA1 Sp1 polymorphism and ultrasound parameters. Presence of the "s" allele as well as low SOS acted as significant predictors of wrist fracture only in heavier women, (> or =62 kg) but not in women with a body weight of less than 62 kg. In heavier women, both the COLIA1 Sp1 polymorphism and ultrasound parameters acted as independent markers that contributed to BMD to enhance fracture prediction. However, the COLIA1 enabled a higher specificity (specificity 72.4%, sensitivity 44.2%), whereas SOS enabled a higher sensitivity (sensitivity 73.9%, specificity, 45.7%). We conclude that BMD at total forearm, the COLIA1 polymorphism, and ultrasound SOS are independent predictors of wrist fracture in postmenopausal women. The effect of the COLIA1 Sp1 polymorphism and SOS on wrist fracture risk is more pronounced in patients with a higher body weight.

The purpose of this cross-sectional case-control study was to determine whether indices of bone structure at the 4% site of the radius discriminate women who have sustained a recent low-energy fracture of the contralateral distal radius (n = 21) from women with similar bone density and no history of fracture (n = 21). Images of the distal forearm were acquired using peripheral quantitative computed tomography (pQCT) and were analyzed using in-house-developed software to determine indices of trabecular bone structure (average hole size [H(A)], maximum hole size, and connectivity index). The same images were analyzed using commercial software to determine bone density, mass, geometry, and torsional strength. The fracture group had significantly larger H(A) (p = 0.03). No other bone variable differed between groups. Individual H(A) values were compared to the mean value for young adult women (n = 42). The odds ratio (95% confidence interval) associated with an H(A) >2 SDs above the young adult mean was 5.4 (1.2-24.3). Thus, estimation of in vivo trabecular bone porosity by measuring the average diameter of the pQCT-imaged marrow spaces in the ultradistal radius identifies individuals with low bone mass most at risk for osteoporotic fracture.

Corticosteroid treatment diminishes bone mass and alters bone quality. The objective was to evaluate bone in corticosteroid-treated patients and controls and in fractured and non-fractured patients treated with corticosteroids using both X-ray densitometry (DEXA) and ultrasound. We evaluated 34 women aged 58 +/- 14 years (X +/- SD), who had been on long-term low dose prednisone therapy for at least 6 months, and who had never received specific treatment for osteoporosis. Bone mineral density of total skeleton (TS), lumbar spine (LS), femoral neck (FN), and vertebral morphometry (MXA) were measured by DEXA. Speed of sound (SOS), broadband ultrasound attenuation (BUA) and stiffness were measured using an Achilles Plus system. Forty-two healthy women served as controls. Both densitometric and ultrasound parameters in the patients were significantly diminished compared with controls: TS: P < 0.002, LS: P < 0.025, FS: P < 0.005, Stiffness: P < 0.001, BUA: P < 0.002 and SOS: P < 0.002. The percentage of patients with a Z score below -2 was higher in Stiffness and BUA: 38% and 47%, respectively, compared with a range of 16-24% in the other parameters (P < 0.05 BUA vs. DEXA measurements). Eleven patients with previous bone fracture had values lower than the non-fractured patients, both according to DEXA and ultrasound measurements, but the difference was only significant for BUA (P < 0.02). BUA of the calcaneus was more effective in detecting the specific skeletal alterations and fracture risk of the group of patients receiving chronic corticosteroid treatment.

Objectives: To evaluate spinal curvature changes over a 3-year period in postmenopausal women who had had an osteoporotic vertebral fracture within the last 3 months., Methods: Thoracic kyphosis and lumbar lordosis were measured using a curviscope at baseline and after 1, 3, 6, 12, and 36 months. Anteroposterior and lateral radiographs of the thoracolumbar spine were obtained after 1 and 3 years., Results: Sixty-one patients were included. At baseline, a significant increase in thoracic curvature was found in the subgroup with thoracic fractures as compared to the subgroups with thoracolumbar or lumbar fractures (64 degrees +/- 9 degrees, 56 degrees +/- 10, and 56 degrees +/- 13, respectively; P < 0.05). No lumbar curvature differences were found. Thoracic curvature was significantly correlated with age (r = -0.48, P < 0.001) and with the vertebral deformity index (r = 0.6, P < 0.001). A significant increase in thoracic curvature was apparent 3 months into the study; after 3 years, the increase was 5.6 degrees +/- 0.7 (P < 0.01). A moderate increase in lumbar curvature was found after 3 years (P < 0.01). Five of 13 patients and five of 10 patients had at least one incident fracture after 1 and 3 years, respectively. Mean thoracic curvature was greater among the patients with than without incident fractures after 1 and 3 years, although the difference was not statistically significant., Conclusion: Thoracic compression fractures significantly increase thoracic kyphosis as compared to dorsolumbar and lumbar fractures. Thoracic kyphosis worsens overtime in patients with prevalent vertebral fractures. These data invite an evaluation of techniques capable of providing early correction of alignment disorders, such as widespread use of bracing or kyphoplasty.

Estrogen therapy decreases bone remodeling, but the association between endogenous estradiol (E2), estrone (E1), testosterone (T), and bone turnover in older women is not clear. To test the association of serum E2, E1, free T, and sex hormone-binding globulin (SHBG) with bone turnover, we analyzed cross-sectional relationships among E2, E1, T, SHBG, and biochemical markers of bone turnover serum osteocalcin [OC], serum bone-specific alkaline phosphatase [bAP], and serum breakdown products of C telopeptide of type I collagen [CTx] in 704 women enrolled in the Study of Osteoporotic Fractures. Women with lower estradiol levels tended to have higher levels of bone turnover, but the association was weak (R(2) = 0.01 for the association E2-OC, p = 0.03; and R(2) = 0.024 for E2-CTx, p = 0.001). Relationships between SHBG and turnover were also weak (R(2) for the association SHBG-OC was 0.07, p < 0.001, and 0.03 for SHBG-sCTx, p = 0.03), or not significant (R(2) < 0.01 for the association SHBG-bAP). Associations of E1 and T with these markers were of the same magnitude. These results were not modified after adjustment for age, weight, and smoking status. We conclude that older women with low endogenous hormones have somewhat higher bone turnover, but these associations are weak. Bone turnover is determined mainly by factors other than endogenous concentrations of sex hormones.

There were studied 453 young servicemen with dyshormonal strain bone disease in whom the hormonal status, state of carbohydrate and protein metabolism were investigated. It was established that in 92.9% of patients the growth hormone--somatotropic hormone (STH) was significantly decreased, production of thyroid hormones necessary for physiologic osteogenesis (T3 and T4) was impaired and albuminous fraction dissociation was revealed. The authors consider that in dyshormonal strain bone disease in young people the insufficiency of hormonal regulation of growth processes and bone regeneration is the primary factor while the physical strain is the additional secondary factor.

Physician awareness of the risk of osteoporosis and subsequent fractures in a patient with a history of long-term steroid treatment is high. The tendency to assume that a fracture is owing to steroid-induced osteoporosis may result in an unnecessarily intense antiresorptive treatment regimen for a patient who may not have osteoporosis. I report here about a patient with rheumatoid arthritis who presented with bone fracture despite antiresorptive therapy and without evidence of osteoporosis by bone mineral density testing.

Patients with end-stage liver disease have low bone-turnover osteoporosis, and there is often further bone loss of 20% to 30% after orthotopic liver transplantation (OLT). Bone recovery after OLT has been reported, but data are limited. We undertook studies to determine whether bone recovery continues in the long term. Twenty-eight adult patients alive at least 5 years after OLT were studied (14 men, 14 women). Bone mineral density (BMD), serum parathyroid hormone (PTH), osteocalcin, and vitamin D levels were measured pretransplantation, at 3 months, 12 months, a mean of 46 months, and a mean of 85 months (range, 63 to 117 months) after transplantation. When BMD is expressed as a z score, the results were as follows: x0.82 +/- 0.22 pre-OLT; -2.04 +/- 0.27 at 3 months; -1.68 +/- 0.24 at 12 months; -1.23 +/- 0.24 at a mean of 46 months; and -1.0 +/- 0.26 at a mean of 85 months after OLT. The results at 46 and 85 months were significantly greater than the measurement at 3 months after OLT (P <.05). Furthermore, mean BMD (expressed as a z score) returns to the pre-OLT level at a mean of 85 months. At final follow-up, 9 of 28 patients had elevated PTH levels, and 14 of 27 patients had elevated osteocalcin levels. Five patients had spontaneous fractures in the first 12 months after transplantation, and 5 more patients had fractures by final follow-up. Even at 7 years after OLT, there was a significant increase in BMD (expressed as a z score) compared with 3 months after transplantation. Elevation of serum PTH and osteocalcin levels in some patients suggests continuing bone remodeling.

Calcaneus bone mineral density (BMD) of 738 Japanese women (605 healthy and 133 with osteoporosis) was measured using single X-ray absorptiometry (SXA). A reference range of calcaneus BMD values for healthy Japanese women was established and the usefulness of this method for screening and diagnosis of osteoporosis was evaluated. There was no significant age change of calcaneus BMD prior to menopause, though values decreased significantly thereafter. BMD loss ratio was 1.7%/year in the 10 years after menopause. The reference range of calcaneus BMD was 410 +/- 43 mg/cm(2), calculated from the mean BMD value of subjects whose ages ranged from 25 to 50 years old. The fracture threshold for the spine was established as 294 mg/cm(2), which corresponded to -2.67 SD from the average BMD of the young healthy women, and the odds ratio for spine fracture in the subjects with BMD lower than this threshold was 3.52 [95% CI (confidence interval) 1.34-9.26]. The spine fracture group showed statistically lower calcaneus BMD than the nonfracture group when subjects with adjusted age and body size were analyzed. There were no significant differences in the ROC analysis for spine fracture between calcaneus BMD and spine BMD. Therefore, calcaneus BMD is not readily affected by degenerative change or soft tissue, and the annual decrement rate (1.7%/year) can be detected easily and with low precision error (0.8%). These indices may prove useful for the screening and diagnosis of osteoporosis.

Objectives: We have previously shown that MS patients have significantly reduced bone mass and a high prevalence of abnormal vitamin D status. The object of this study was to characterize the frequency of adulthood fractures in MS patients, prospectively determine rates of bone loss in MS, and determine whether vitamin D status is a predictor of bone loss., Methods: MS patients (36 women, 18 men) were compared with age- and gender-matched healthy controls (35 women, 14 men). Bone mass was performed by dual x-ray absorptiometry at baseline and at 12-month intervals over 2 years., Results: Fractures in the absence of major trauma had occurred in 2% of controls and 22% of MS patients (p < 0.002). Over the 2 years of prospective follow-up, both women and men with MS lost substantially more bone in the femoral neck than did controls (3% and 6% per year in pre- and postmenopausal women with MS versus 0.5% and 0.8% per year in controls; 7.3% per year in men with MS versus 1.6% per year in controls). Bone loss in the spine was also greater in women with MS than in controls (1.6 to 3.5% per year loss in MS patients versus no change in controls). Duration of steroid treatment beyond 5 months and ambulatory status were both predictors of bone loss. Bone loss in the spine occurred faster in MS patients with low (<20 ng/mL) 25-hydroxyvitamin D levels (1.9% per year, p < 0.04), whereas in those with normal 25-hydroxyvitamin D levels, bone loss was insignificant. At the femoral neck, bone loss was substantial in all patients, but was somewhat faster in the group with low levels of 25-hydroxyvitamin D (5.6% per year, p < 0.0001) compared with the group with high levels of 25-hydroxyvitamin D (4.3% per year, p = 0.03)., Conclusions: MS patients have more frequent fractures and lose bone mass more rapidly than do their healthy age- and gender-matched peers, in part related to insufficient vitamin D. Vitamin D repletion in MS patients who are deficient might reduce, to some extent, the rate of bone loss and decrease osteoporosis-related fractures.

Osteoporosis is common in patients with chronic cholestatic liver disease, and atraumatic spinal fracture is a recognized complication after orthotopic liver transplantation. Bisphosphonates are potent inhibitors of osteoclast bone resorption and have been successfully used to treat postmenopausal osteoporosis. We examined whether preoperative bone mineral density can predict the risk of fracture after orthotopic liver transplantation and whether intravenous bisphosphonate can prevent fractures in high-risk patients. Beginning in February 1993, standard bone mineral density measurements of the lumbar spine were performed as part of routine pretransplantation assessment. On the basis of a preliminary analysis from January 1995, patients with a lumbar spine bone mineral density of <0.84 g/cm2, or <84% of the predicted value (age/sex), were treated with intravenous bisphosphonate (pamidronate disodium) every 3 months before and for 9 months after liver transplantation. Bone mineral density measurements were available in 90 of 136 consecutive first transplants performed in our unit from February 1993 to September 1996. Before the use of pamidronate, 7 patients sustained symptomatic vertebral fractures. Their mean spine bone mineral density was lower than in the 38 patients with no clinical evidence of fracture (81.8% +/- 12.3% v 94.2% +/- 10.2%; P = .006). Since the introduction of pamidronate, no symptomatic vertebral fractures have occurred. Of 29 surviving patients with bone mineral density <0.84 g/cm2 before transplantation, 38% who did not receive treatment with pamidronate suffered spontaneous fracture, whereas 0 of 13 who received treatment suffered such a complication. A low lumbar spine bone mineral density is associated with a high risk of symptomatic vertebral fracture after liver transplantation. These results suggest that this risk is considerably reduced by the administration of intravenous bisphosphonate before and after transplantation.

Study Design: Thoracic vertebrae were subjected to compressive loads after drilling of the centrum to simulate destruction from metastatic tumorous involvement., Objective: To determine whether a threshold exists that is predictive of fractures to establish a correlation between significant variables and vertebral strength., Summary of Background Data: The mechanical effects of metastatic destruction of thoracic vertebral bodies and their correlation to pathologic fractures has been analyzed in few studies. In additional studies on intact vertebral strength, investigators have determined that bone mineral density and geometric factors are important., Method: Fifty-four cadaveric thoracic vertebrae were studied. All were examined by quantitative computed tomography. T4 and T10 served as mechanical controls to predict the intact strength of T7. The test vertebrae were drilled from the anterior cortex through to the posterior cortex before they were loaded., Results: Linear correlation between the strength of T4 and T10 in each spine supported the predicted strengths of T7. Because of variation from other factors, no threshold defect size was noted beyond which failure consistently occurred. Results of linear correlation analyses showed that the best combination of parameters for predicting vertebral strength was the product of bone mineral density and the remaining intact vertebral body cross-sectional area. This vertebral strength index correlated linearly with the strength of intact and compromised T7 vertebrae (r2 = 0.52)., Conclusions: The vertebral strength index can be used to predict the strength of any thoracic vertebra. When compared with an idealized vertebral strength index based on the intact vertebral cross-sectional area and normal bone mineral density, a patient's actual vertebral strength index can be used as one of the criteria for prophylactic stabilization.

Insufficiency fractures often occur in the sacrum and pubic rami but have rarely been reported in the ilium, where their frequency may be underestimated. We studied a series of 14 patients with insufficiency fractures of the ilium. Six patients had an oblique fracture through the wing of the ilium (which was bilateral in one case) and nine a supraacetabular fracture, with in one case a superomedial extension into the iliac wing. The initial radiographs were normal, making the diagnosis difficult. A linear area of sclerosis along the fracture line was seen after a few weeks. The radionuclide examination provided early detection and often demonstrated multiple insufficiency fractures (mean 2.1 per patient). Computed tomography missed some of the fractures, whereas magnetic resonance imaging proved a reliable diagnostic tool, especially in patients with supraacetabular fractures, showing the fracture as a line of low signal surrounded by an area of edema whose contours were exactly the same as those of the hyperactive focus on the radionuclide scan. Osteoporosis was a causative factor in all 14 patients and vitamin D deficiency in seven. Also, three patients had a history of fluoride therapy.

Objective: Vertebral fracture is the most frequent manifestation of osteoporosis in women. Because there is a lack of information about bone density and the occurrence of fractures in men with osteoporosis, we evaluated the relationship between vertebral fractures and spinal bone mineral density (BMD) to determine if there is a threshold of BMD below which fractures are likely to occur., Subjects and Methods: Radiographs of the spine and BMD measurements of the lumbar spine as measured by quantitative CT were obtained in 201 men 21-86 years old (mean age, 68 +/- 4 years) who were referred consecutively for osteoporosis screening. Radiographs were interpreted for the presence or absence of vertebral fractures. The probability of fractures was determined after classifying the patients into subgroups according to their quantitative CT values. The relationship of spinal bone mass to spinal fracture was examined by both logistic regression and receiver operating characteristic (ROC) analysis., Results: Seventy-one patients were classified as having definite vertebral compression fractures. Spinal BMD was 132 +/- 34 mg/ml for the 130 men without vertebral fractures and 75 +/- 22 mg/ml for the 71 men with vertebral fractures (p < .001). The number of fractures per patient and the BMD were negatively correlated (r = -0.71, p < 0.0001). When a BMD of 100 mg/ml was given as a fracture threshold, 15% of the patients without fractures were below this value and 14% of the patients with fractures were above this threshold. Quantifying the overlap between values from patients with and without fractures by ROC analysis, the value of 100 mg/ml gave a sensitivity of 86%. Logistic regression showed 105 mg/ml as the most discriminate value, resulting in a sensitivity of 90%. Logistic regression analysis of the predicted fracture probability also indicated that age does not significantly influence the regression curve., Conclusion: We found that direct quantitative CT measurement of the BMD of the vertebral body is a highly efficient approach to distinguish men without vertebral fractures from those with fractures. Thus, a fracture-threshold concept could provide a quantitative criterion to identify men at high risk for vertebral fractures.

We report a patient with severe chronic renal failure who developed spontaneous bone fractures. He was found to have hypercalcemia, normal calcitriol levels (probably due to extrarenal production by noncaseating granulomas), and functional hypoparathyroidism. The bone biopsy showed low bone turn-over and the presence of noncaseating granulomas. Treatment with corticosteroids decreased the calcium and calcitriol levels and the parathyroid hormone levels rose. No further fractures occurred. A repeat bone biopsy revealed the presence of osteitis fibrosa. Renal osteodystrophy may be modulated by extrarenal production of calcitriol. In this case, excessive suppression of parathyroid hormone by endogenous calcitriol presumably caused an adynamic bone lesion and spontaneous fractures.

The objective was to study the dose-related response of intranasal salmon calcitonin (Salcatonin) on bone mass and bone turnover and the effect of salcatonin on rates of fracture in elderly women with moderate osteoporosis. A total of 208 healthy women aged 68-72 years, who had a bone mineral content (BMC) of the distal forearm 30% below the mean value for healthy premenopausal women, were examined in a double-blind, placebo-controlled, randomized group comparison study. They were randomized to a two-year daily treatment of either 50 IU, 100 IU, 200 IU Salcatonin or placebo. All received 500 mg calcium daily. In the calcium-(placebo)-treated group the BMC of the spine increased 1%, whereas an increase of 3% was seen in the 200 IU Salcatonin treated group. There was a dose-related response to Salcatonin manifested by an increase in BMC of 1.0%/100 IU. The incidence of new fractures was significantly lower in the women treated with Salcatonin (about one third of that in the non-Salcatonin treated women). In conclusion the results suggest that, compared with calcium alone, Salcatonin given intranasally reduces the rate of fracture by two thirds in elderly women with moderate osteoporosis. Furthermore, it increases spinal bone mass in a dose dependent manner.