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There is limited research which examines health concerns of individuals with osteogenesis imperfecta (OI). Discussion groups with leaders of the adult OI community identified a broad range of medical priorities beyond fractures and brittle bones. Our work underscores the need to include patient-reported outcomes in rare bone disease research., Introduction: Osteogenesis imperfecta (OI) is a rare genetic disorder affecting collagen protein leading to brittle bones and a number of other medical complications. To date, there is limited research which examines the life-long process of aging with this rare disease, much less the perspective of individuals with OI., Methods: In order to explore and prioritize health concerns that adults with OI feel have been inadequately addressed in health care and research, investigators held discussions with leaders from the global adult OI community. The meetings were held in August 2017 at the 13th International Conference on OI in Oslo, Norway as part of the preconference seminar "Patient Participation in OI Research". Investigators were part of the Brittle Bone Disease Consortium (BBDC), a multicenter research program devoted to the study of OI, and their focus was on patient-reported outcomes (PRO)., Results: Participants noted that while fractures and brittle bones are the most common feature of OI, a number of body systems are under-studied in this disorder. They particularly emphasized breathing, hearing, and the effects of aging as primary concerns that researchers and physicians may not fully understand or address. Other areas included pain, gastrointestinal problems, mental health, nutrition, menopause/pregnancy, and basilar invagination. Participants also emphasized that they must be informed of study results. They underscored that outcome measures incorporated into future drug trials must look beyond fractures and consider the whole patient., Conclusions: This work will help guide the incorporation of PROs into the next phase of the BBDC Natural History Study of OI and underscores the importance of including PROs in the study of rare diseases.

The incidence of atypical femoral fractures (AFFs) was 2.95% among 6644 hip and femoral fractures. Independent risk factors included the use of bisphosphonates (BPs), osteopenia or osteoporosis, rheumatoid arthritis, increased femoral curvatures, and thicker femoral cortices. Patients with AFFs and BP treatment were more likely to have problematic healing than those with typical femoral fractures (TFFs) and no BP treatment., Introduction: To determine the incidence and risk factors of atypical femoral fractures (AFFs), we performed a multicenter case-control study. We also investigated the effects of bisphosphonates (BPs) on AFF healing., Methods: We retrospectively reviewed the medical records and radiographs of 6644 hip and femoral fractures of patients from eight tertiary referral hospitals. All the radiographs were reviewed to distinguish AFFs from TFFs. Univariate and multivariate logistic regression analyses were performed to identify risk factors, and interaction analyses were used to investigate the effects of BPs on fracture healing., Results: The incidence of AFFs among 6644 hip and femoral fractures was 2.95% (90 subtrochanter and 106 femoral shaft fractures). All patients were females with a mean age of 72 years, and 75.5% were exposed to BPs for an average duration of 5.2 years (range, 1-17 years). The use of BPs was significantly associated with AFFs (p < 0.001, odds ratio = 25.65; 95% confidence interval = 10.74-61.28). Other independent risk factors for AFFs included osteopenia or osteoporosis, rheumatoid arthritis, increased anterior and lateral femoral curvatures, and thicker lateral femoral cortex at the shaft level. Interaction analyses showed that patients with AFFs using BPs had a significantly higher risk of problematic fracture healing than those with TFFs and no BP treatment., Conclusions: The incidence of AFFs among 6644 hip and femoral fractures was 2.95%. Osteopenia or osteoporosis, use of BPs, rheumatoid arthritis, increased anterior and lateral femoral curvatures, and thicker lateral femoral cortex were independent risk factors for the development of AFFs. Patients with AFFs and BP treatment were more likely to have problematic fracture healing than those with TFFs and no BP treatment.

Risk for subtrochanteric and diaphyseal femoral fractures is considered increased in patients with hypophosphatasia (HPP). Evaluating a large cohort of HPP patients, we could for the first time quantify the prevalcence and identify both morphometric features as well as predisposing factors for this complication of severe HPP., Introduction: Subtrochanteric and diaphyseal femoral fractures have been associated with both, long-term antiresorptive treatment and metabolic bone disorders, specifically Hypophosphatasia (HPP). Building on a cross-sectional evaluation of real-world data, this study reports risk factors, prevalence, treatment outcome and morphometric particularities for such fractures in HPP as compared to Atypical Femoral Fractures (AFF) in long-term antiresorptive treatment., Methods: For 15 out of 150 HPP patients identified with having experienced at least one such fracture, medical records were reviewed in detail, extracting medical history, genotype, lab assessments, bone mineral density (DXA), radiographic data on femoral geometry and clinical aspects of fracture etiology and healing., Results: Bilateral fractures were documented in 10 of these 15 patients, yielding a total of 25 fractures for evaluation. Disease-inherent risk factors included autosomal-recessive, childhood onset HPP, apparently low alkaline phosphatase (ALP) ≤ 20 U/l and substantially elevated pyridoxal 5'-phosphate (PLP) > 3 times upper limit of normal as well as high lumbar spine BMD. Fracture morphology met definition criteria for AFF in 88% of cases. Femoral geometry revealed additional risk factors previously described for AFF, including decreased femoral neck-shaft angle and increased femoral offset. Extrinsic risk factors include Hypovitaminosis D (80%) and pre-treatment with bisphosphonates (46,7%) and Proton-Pump Inhibitors (40%)., Conclusions: Increased risk for subtrochanteric and diaphyseal femoral fractures in HPP appears to result from both compromised bone metabolism as well as disease-associated bone deformities. In severe HPP, generous screening for such fractures seems advisable. Bisphosphonates and Hypovitaminosis D should be avoided. Healing is compromised and requires mindful consideration of both pharmacological and surgical options.

Objectives: Corticosteroid treatment of paediatric leukaemia patients can lead to osteonecrosis (ON). We determined whether bone marrow oedema (BME) is an early sign of progressive ON and eventual bone collapse., Methods: In a retrospective study, two radiologists reviewed MR imaging characteristics of 47 early stage epiphyseal ON in 15 paediatric and adolescent leukaemia patients. Associations between BME on initial imaging studies and subchondral fracture, disease progression and bone collapse were assessed by Cochran-Mantel-Haenszel tests. Differences in time to progression and bone collapse between lesions with and without oedema were assessed by log rank tests., Results: Forty-seven occurrences of ON were located in weight bearing joints, with 77% occurring in the femur. Seventeen lesions progressed to collapse, two lesions worsened without collapse, and 28 remained stable or improved. BME was significantly associated with subchondral fracture (p = 0.0014), disease progression (p = 0.0015), and bone collapse (p < 0.001), with a sensitivity and specificity of 94% and 77%, respectively, for bone collapse. Time to progression for ON with oedema was 2.7 years (95% CI: 1.7-3.4); while the majority of no-oedema ON were stable (p = 0.0011)., Conclusions: BME is an early sign of progressive ON and eventual bone collapse in paediatric and adolescent leukaemia patients., Key Points: • Bone marrow oedema in corticosteroid-induced osteonecrosis predicts progression to bone collapse. • Bone marrow oedema is associated with subchondral fractures in corticosteroid-induced osteonecrosis. • Bone marrow oedema can be used to stratify patients to joint-preserving interventions. • Absence of bone marrow oedema can justify a "wait and watch" approach.

Osteogenesis imperfecta (OI) is typically characterized by low bone mass and increased bone fragility caused by heterozygous mutations in the type I procollagen genes (COL1A1/COL1A2). We report two cases of a 56-year-old woman and her 80-year-old mother who suffered from multiple vertebral and non-vertebral fractures with onset in early childhood. A full osteologic assessment including dual-energy X-ray absorptiometry (DXA), high-resolution peripheral quantitative computed tomography (HR-pQCT), and serum analyses pointed to a high bone mineral density (BMD) in the hip (DXA Z-score + 3.7 and + 3.9) but low to normal bone mass in the spine and preserved bone microstructure in the distal tibia. Serum markers of bone formation and bone resorption were elevated. Using whole exome sequencing, we identified a novel mutation in the COL1A2 gene causing a p. (Asp1120Gly) substitution at the protein level and affecting the type I procollagen C-propeptide cleavage site. In line with previously reported cases, our data independently prove the existence of an unusual phenotype of high bone mass OI caused by a mutation in the procollagen C-propeptide cleavage with a clinically persistent phenotype through adulthood.

In this study, we report on clinical, radiographic and biochemical characteristics of 38 patients with adult hypophosphatasia. High-resolution peripheral quantitative computed tomography showed alterations of bone microstructure in a subgroup of 14 patients. Pyridoxal-5-phosphate levels correlated with the occurrence of fractures and the number of symptoms., Introduction: Hypophosphatasia (HPP) is a rare disorder with a wide range of clinical manifestations. A reduced enzymatic activity of alkaline phosphatase (ALP) is the key marker of the disease, causing an accumulation of ALP substrates such as pyridoxal-5-phosphate (PLP). The purpose of this retrospective study was to further characterize adult onset HPP., Methods: We assessed clinical, radiographic and laboratory characteristics of 38 adult patients with HPP. Diagnosis of HPP was established by the combination of low-serum ALP, raised PLP levels and typical symptoms and was genetically confirmed in 32 patients. Dual-energy X-ray absorptiometry (DXA) and laboratory data were available in most patients. High-resolution peripheral quantitative computed tomography (HR-pQCT) was performed in 14 patients., Results: Clinical characteristics included a wide spectrum of symptoms. A history of fracture was present in 15 patients (39%). Twenty-one patients (55%) complained about recurring headaches, 23 patients (61%) had recurring muscle pain, 4 patients (11%) suffered from severe muscle weakness and 18 patients (47%) showed dental abnormalities. Z-scores assessed by DXA were only slightly reduced in most adult HPP patients. HR-pQCT of 14 patients showed microstructural changes of trabecular and cortical bone compared to reference values of healthy subjects. The occurrence of fractures and multiple symptoms (>2 typical HPP symptoms) were associated with significantly elevated levels of PLP., Conclusion: Adult HPP presents with a wide range of clinical symptoms and is not associated with low bone mass in general. PLP seems to be a good marker for disease severity in adult patients as its level is correlated with the occurrence of fractures and number of symptoms.

In 26 of 94 individuals (28%) below 21 years of age who had a significant fracture history but did not have extraskeletal features of osteogenesis imperfecta (OI), we detected disease-causing mutations in OI-associated genes., Introduction: In children who have mild bone fragility but do not have extraskeletal features of OI, it can be difficult to establish a diagnosis on clinical grounds. Here, we assessed the diagnostic yield of genetic testing in this context, by sequencing a panel of genes that are associated with OI., Methods: DNA sequence analysis was performed on 94 individuals below 21 years of age who had a significant fracture history but had white sclera and no signs of dentinogenesis imperfecta., Results: Disease-causing variants were detected in 28% of individuals and affected 5 different genes. Twelve individuals had mutations in COL1A1 or COL1A2, 8 in LRP5, 4 in BMP1, and 2 in PLS3., Conclusions: DNA sequence analysis of currently known OI-associated genes identified disease-causing variants in more than a quarter of individuals with a significant fracture history but without extraskeletal manifestations of OI.

The majority of tumor-induced osteomalacia cases have been reported in the Northern Hemisphere and Asia. In this first series of South American patients, we show that the clinical presentation and sensitivity of plasmatic fibroblast growth factor 23 and somatostatin analog-based imaging are similar to those described in other populations., Introduction: Describe the experience of clinical presentation, diagnostic study, and treatment of patients with tumor-induced osteomalacia (TIO) in a South American academic center in comparison to literature., Methods: Analysis of the records of patients diagnosed with TIO. The clinical presentation, diagnostic studies, and treatment were analyzed. Fibroblast growth factor 23 (FGF23) was measured by ELISA., Results: Six patients were diagnosed with TIO during the studied period. The patients' median age was 53 years (range 22-64). All patients presented with weakness and pain in the extremities. Four experienced fractures during their evolution. The median time to diagnosis was 4.5 years (1-20). Biochemical studies showed hypophosphatemia, median of 1.4 mg/dL (1.2-1.6), with low maximum rates of tubular reabsorption of phosphate adjusted for glomerular filtration rate. FGF23 was elevated in 4/6 patients and inappropriately normal in the other two. In three patients, the location of the tumor was clinically evident and confirmed with anatomical imaging. In the remaining patients, two tumors were located with 68 Ga DOTATATE-PET/CT and one with OctreoScan. The causal tumors were located in the lower extremities in five patients and invading the frontal sinus in one patient. In all patients, tumors were successfully removed. Within 14 days, there was normalization of phosphate and FGF23 levels and resolution of clinical symptoms in all patients. In all cases, the histopathology was compatible with a phosphaturic mesenchymal tumor., Conclusions: The clinical presentation, delay time to diagnosis, FGF23 diagnostic sensitivity and histopathology in this first series of South American patients is similar to those described in other populations. The success of localization by somatostatin analog-based imaging, suggests this may the optimal imaging modality.

In clinical practice, areal bone mineral density (aBMD) is usually measured using dual-energy X-ray absorptiometry (DXA) to assess bone status in patients with or without osteoporotic fracture. As BMD has a Gaussian distribution, it is difficult to define a cutoff for osteoporosis diagnosis. Based on epidemiological considerations, WHO defined a DXA-based osteoporosis diagnosis with a T-score <-2.5. However, the majority of individuals who have low-trauma fractures do not have osteoporosis with DXA (i.e., T-score <-2.5), and some of them have no decreased BMD at all. Some medical conditions (spondyloarthropathies, chronic kidney disease and mineral bone disorder, diabetes, obesity) or drugs (glucocorticoids, aromatase inhibitors) are more prone to cause fractures with subnormal BMD. In the situation of fragility fractures with subnormal or normal BMD, clinicians face a difficulty as almost all the pharmacologic treatments have proved their efficacy in patients with low BMD. However, some data are available in post hoc analyses in patients with T score >-2. Overall, in patients with a previous fragility fracture (especially vertebra or hip), treatments appear to be effective. Thus, the authors recommend treating some patients with a major fragility fracture even if areal BMD T score is above -2.5.

Incidence of fragility fracture of a population-based cohort of 345 patients with sarcoidosis was compared with age and sex-matched comparators. The incidence of fragility fracture was higher among patients with sarcoidosis with hazard ratio (HR) of 2.18., Introduction: Several chronic inflammatory disorders increase the risk of fragility fracture. However, little is known about the risk of fragility fracture in patients with sarcoidosis., Methods: This study was conducted using a previously identified population-based cohort of 345 patients with incident sarcoidosis from Olmsted County, Minnesota. Diagnosis of sarcoidosis required physician diagnosis supported by biopsy showing non-caseating granuloma, radiographic evidence of intrathoracic sarcoidosis, and compatible clinical presentations without evidence of other granulomatous diseases. Sex and age-matched subjects randomly selected from the same underlying population were used as comparators. Medical records of cases and comparators were reviewed for baseline characteristics and incident fragility fracture., Results: Fragility fractures were observed in 34 patients with sarcoidosis, corresponding to a cumulative incidence of 5.6% at 10 years, while 18 fragility fractures were observed among comparators for a cumulative incidence of 2.4% at 10 years. The HR of fragility fractures among cases compared with comparators was 2.18 (95% confidence interval [CI], 1.23-3.88). The risk of fragility fracture by site was significantly higher among patients with sarcoidosis, and was due to a higher rate of distal forearm fracture (HR 3.58; 95% CI 1.53-8.40). Statistically non-significant increased risk was also observed in proximal femur (HR 1.66; 95% CI 0.45-6.06) and proximal humerus (HR 3.27; 95% CI 0.66-16.21). Risk of vertebral fracture was not increased (HR 1.00; 95% CI 0.32-3.11)., Conclusion: Patients with sarcoidosis have an increased risk of fragility fracture which is primarily driven by the higher incidence of distal forearm fracture.

Objective: To compare the efficacy of percutaneous long bone cementoplasty (PLBC) with and without embedding a cement-filled catheter in the medullary canal (ECFC) for painful long bone metastases with impending fracture., Methods: A retrospective study was conducted in 36 consecutive patients undergoing PLBC and ECFC combination (n = 17, group A) or PLBC alone (n = 19, group B). All patients had a high risk of impending fracture in the long bone based on Mirels' scoring system. Clinical effects were evaluated using both a pre- and a postoperative visual analogue scale (VAS) and Karnofsky performance scale (KPS)., Results: Overall pain relief rate with excellent (VAS 0-2) and good (VAS 2.5-4.5) results during follow-up was significantly higher in group A than in group B (88.2 % vs. 57.9 %, P<0.05). The average VAS and KPS changes in group A were significantly higher than those in group B at 1, 3 and 6 months postoperatively (P<0.05). Also, the rate of fractures of the treated long bone in group A was significantly lower than that in group B (P<0.05)., Conclusions: Combined PLBC and ECFC is a safe and effective procedure for long bone metastases with impending fracture., Key Points: • Metastases in long bones may cause pain and subsequent pathological fractures. • Cementoplasty resulted in significant pain relief in patients with long bone metastases. • Combination of PLBC and ECFC may reduce the incidence of fractures.

Osteoporosis treatments are usually given for a limited period of time in order to balance benefits and risks. We report three cases of postmenopausal women without any previous fragility fracture who presented severe spontaneous vertebral fractures after denosumab discontinuation. We think that the occurrence of these fractures could be explained by the severe rebound effect observed after denosumab discontinuation and that a consensus regarding the end of treatment with denosumab has to be defined.

Summary: Low serum total alkaline phosphatase level (ALP), the hallmark for hypophosphatasia (HPP), must be recognized to provide appropriate care of the patients and to avoid antiresorptive treatment. The prevalence of persistent low ALP in a clinical setting is 0.13% and the recognition is very low (3%)., Introduction: A low serum total alkaline phosphatase level is the hallmark for the diagnosis of hypophosphatasia. Although very rare, HPP must be recognized to provide appropriate treatment of non-union fractures and to avoid potentially harmful drugs, such as antiresorptive treatments. The aim of this study was to assess the recognition of persistent low ALP in a tertiary care hospital., Methods: Between the 1st of January and the 31st of December 2013, 48,755 patients had ALP assessment in the Biochemistry Department of our hospital. Sixty-eight patients had all serum ALP values persistently below 40 IU/l. Among them, six had potential causes of secondary hypophosphatasia. We consulted the summary discharges of the 62 patients in order to check for the notation of low ALP. Patients from the departments of rheumatology and internal medicine were contacted to fulfill a questionnaire about clinical manifestations potentially related to HPP., Results: 0.13% of hospitalized patients had persistently low value. They were 46.5 ± 17.7 years old, and 73% were females. The low ALP value was notified in the discharge summary for two patients (3%), without any comment. Twenty-four patients (46 + /-16 years old) were contacted. Eight patients had fractures; two had a diagnosis of rickets in the childhood; two had symptomatic chondrocalcinosis. Nine had dental abnormalities. Three were receiving a bisphosphonate; two of them had a fracture while being treated with bisphosphonate., Conclusion: Our study shows that low ALP is not recognized in a clinical setting in adults hospitalized in a tertiary care hospital.

Pycnodysostosis is a rare autosomal recessive disease due to a mutation in the gene for the enzyme Cathepsin K. It is characterized by short stature, craniofacial dysmorphias, osteosclerosis, and brittle bones. There are only a few reports in the literature describing surgical interventions for long bone fractures in pycnodysostosis patients, most of which describe intramedullary nail treatment of isolated long bone fractures. We describe a case in which a pregnant female with pycnodysostosis presented with a shaft fracture of the left femur following minor trauma and a history of increasing thigh pain. Radiographs obtained in the emergency room also revealed an impending subtrochanteric fracture of the contralateral side. The acute left femoral shaft fracture was treated with an adolescent-sized intramedullary nail; it was decided to defer surgery on the contralateral side until after pregnancy. Three months later, the patient had the contralateral femur prophylactically fixated with a plate and screws. One year after the index surgery, both methods demonstrated satisfactory healing both clinically and radiographically. Although we recommend use of an intramedullary nail for long bone fractures in patients with pycnodysostosis, a plate can be utilized if health conditions or skeletal morphology precludes use of a nail.

Objectives: To quantitatively evaluate cartilage repair after microfracture (MF) for ankle osteochondritis dissecans (OCD) using MRI and analyse correlations between MRI and clinical outcome., Methods: Forty-eight patients were recruited and underwent MR imaging, including 3D-DESS, T2-mapping and T2-STIR sequences, and completed American Orthopaedic Foot and Ankle Society (AOFAS) scoring. Thickness index, T2 index of repair tissue (RT) and volume of subchondral bone marrow oedema (BME) were calculated. Subjects were divided into two groups: group A (3-12 months post-op), and group B (12-24 months post-op). Student's t test was used to compare the MRI and AOFAS score between two groups and Pearson's correlation coefficient to analyse correlations between them., Results: Thickness index and AOFAS score of group B were higher than group A (P < 0.001, P < 0.001). T2 index and BME of group B were lower than group A (P < 0.001, P = 0.012). Thickness index, T2 index and BME were all correlated with AOFAS score (r = 0.416, r = -0.475, r = -0.353), but BME was correlated with neither thickness index nor T2 index., Conclusions: Significant improvement from MF can be expected on the basis of the outcomes of quantitative MRI and AOFAS score. MRI was correlated with AOFAS score. BME is insufficient as an independent predictor to evaluate repair quality, but reduction of BME can improve the patient's clinical outcome., Key Points: • Patients with unstable ankle OCD had satisfactory clinical outcome after MF. • Quantitative MRI correlates with clinical outcome after MF for ankle OCD. • The reduction of subchondral BME will improve the patient's clinical outcome. • Quantitative MRI can monitor the process of cartilage repair over time.

Fibrogenesis imperfecta is an extremely rare acquired progressive bone disorder of unknown etiology. In its course, normal bone architecture is replaced at sites by structurally unsound collagen-deficient tissue resulting in a disorganized bone structure and a skeleton that is radically susceptible to deformity and fracture. Herein, we report the case of a patient who had experienced constant bone pain and several spontaneous fractures since 1997. In 10 years' time with the sole exception of his skull, the disease affected the entire skeleton causing a significant decrease in height and progressive disablement. Laboratory findings included elevation of serum alkaline phosphatase and C-terminal telopeptide of type 1 collagen, with normal serum calcium, phosphate, 25-hydroxy-vitamin-D, and parathyroid hormone concentrations. Monoclonal gammopathy was present with no pathological plasma cells in bone marrow. Radiological and histological results were inconclusive suggesting either osteoporosis, osteomalacia, or Paget's disease and later on osteosclerosis. Treatment administered for the abovementioned conditions has proven to be of no effect. The findings eventually raised the possibility of fibrogenesis imperfecta ossium, which was confirmed by polarized light microscopy as well as transmission electron microscopy. The suggested therapy for the disease is melphalan that could not be initiated due to legal restrictions. Steroid monotherapy also reported to be moderately successful in one case resulted in no improvement. Paraproteinemia had been suggested not only to be a characteristic feature but also a possible etiological factor in this condition. In 2012, plasmapheresis was initiated monthly at the beginning, later on biweekly. In response, the patient's symptoms improved dramatically supporting the abovementioned theory.

Purpose: Bone metastases occur in 65-75% of patients with metastatic breast cancer. These patients are at risk of developing skeletal-related events (SREs). SREs are defined as any pathological fracture, spinal cord compression, hypercalcemia, and surgery or radiation required for treatment of bone metastases. Bisphosphonates are used to prevent the development of SREs. The purpose of this study is to review the incidence of SREs in metastatic breast cancer patients with bony disease in Newfoundland and Labrador and to determine if there is an association between SREs and the type of bisphosphonate therapy given., Methods: This retrospective chart review includes all metastatic breast cancer patients with bony disease treated at the Dr. H. Bliss Murphy Cancer Centre from 2008 to 2010. Patient demographics, treatment received, and treatment changes were collected. Patients at the Centre received bisphosphonate, pamidronate or zolendronic acid to prevent SREs. The prescribing pattern of bisphosphonates was collected. The occurrences of SREs were then compared to the type of treatment received., Results: Sixty-five patients with breast cancer and bony metastasis were identified using the provincial tumor registry, three patients were excluded from the review as their charts could not be located. Following the initial diagnosis of bone metastasis, 8 patients (12.7%) were started on zolendronic acid, 50 patients (80.6%) were started on pamidronate, and 4 (6.4%) received no treatment. Six patients (75%) on zolendronic acid experienced one SRE; however, none experienced multiple SREs. Thirty-one patients (62%) on pamidronate experienced one SRE, and ten (20%) had multiple SREs. Of the 31 patients on pamidronate with an SRE, 4 (12.9%) were switched to zolendronic acid. Three of the four (75%) had multiple SREs despite treatment changes. Of the six patients on zolendronic acid with SREs, none were switched to pamidronate., Conclusion: Our results show that the majority of patients with breast cancer, who develop bony metastases in Newfoundland and Labrador, are initially treated with the bisphosphonate, pamidronate. Over 60% of these patients experienced at least one SRE, and 20% had more than two SREs. A small proportion of the patients were initially started on zolendronic acid, and this group had better outcomes with fewer SREs and none had more than two SREs. It appears that zolendronic acid is superior to pamidronate in preventing SREs; however, zolendronic acid is being used primarily as second-line in Newfoundland and Labrador.

To study the role of surgery for symptom palliation in patients with advanced head and neck malignancy. Between 2000 and 2011, patients with locoregionally advanced cancer in the head and neck region, who chose surgical palliation for symptom control, were studied retrospectively. During the study period, 52 patients were included. The index tumour included carcinoma of the maxilla (23.1 %), tongue (19.2 %), larynx/hypopharynx (15.4 %), post-radiation sarcoma (11.5 %), primary sarcoma (11.5 %), carcinoma of the lower alveolus (11.5 %), nasal mucosal melanoma (3.9 %) and metastatic tumour in the head and neck region (3.9 %). The major symptoms included bleeding (53.9 %), tumour pain (19.2 %), dysphagia (11.5 %), non-healing ulcerations (7.7 %), airway obstruction (5.8 %) and pathological fracture of the mandible (1.9 %). Ligation of the carotid artery was performed in 10 patients, complete resection of tumour in 35, and surgical debulking of the tumour in 7 patients. Mean survival of the patients was 5.6 months. The majority of the patients achieved satisfactory and persistent control of symptoms. One patient died from pneumonia during the hospital stay, and the rest were discharged after a mean duration of 16.4 days. In selected patients, surgery is effective in palliating symptoms which are otherwise difficult to manage. Detailed planning and good communication is the key to success in improving the quality of dying.

Unlabelled: We examined patients' communication about fragility fractures to gain insight into why patients do not connect fractures to bone health. The term "fragility" fracture was a misnomer to patients who perceived the event as physically and emotionally traumatic. Improved communication about such fractures could facilitate awareness of bone health., Introduction: We examined patients' communication about fragility fractures to gain insight into why patients do not perceive the connection between their fracture and low bone mass., Methods: A descriptive phenomenological (qualitative) study was conducted. During face-to-face interviews, the participants described the experience of their fracture in detail and the circumstances surrounding the fracture. Data analysis was guided by Giorgi's methodology. English-speaking male and female patients aged 65+ years and "high" risk for future fracture were eligible and screened for osteoporosis through an established screening program at an urban teaching hospital., Results: We recruited 30 participants (9 males, 21 females), aged 65-88, who presented with a hip (n = 11), wrist (n = 11), shoulder (n = 6), or other (n = 2) fracture. Ten of the 30 fractures occurred inside the home and the remaining fractures occurred outside the home. Sustaining a fragility fracture was perceived as a traumatic event, both physically and emotionally. In general, participants used forceful, action-oriented words and referred to hard surfaces to describe the experience. Explanations for the fracture, other than bone quality, were often reported, especially that falls were "freak" or "fluke" events. Patients who sustained a fracture under more mundane circumstances seemed more likely to perceive a connection between the fracture and their bone health., Conclusions: The term fragility fracture was a misnomer for many older adults. By reexamining how this term is communicated to fracture patients, health care providers may better facilitate patients' awareness of bone health.

Sarcoidosis with osseous involvement as the initial manifestation is rare. Due to lack of other organ involvements, the diagnosis is somehow difficult to establish. We report a case with osseous sarcoidosis as the initial and major manifestation that developed spontaneous bone fracture. Our case emphasizes the importance of histological evidence and exclusion of other diseases i.e. rheumatoid arthritis, before making the diagnosis of osseous sarcoidosis.

Summary: We measured bone properties by phalangeal quantitative ultrasound in 1,719 pediatric patients with bone disorders, classifying them according to fracture status. Quantitative ultrasound discriminated fractured and nonfractured pediatric patients and enabled us to stratify fractured patients into classes according to the severity of the causative trauma (spontaneous, minimal trauma, appropriate trauma fractures)., Introduction: The correlation between quantitative bone measurements and fractures is poorly established in pediatric patients with bone disorders. We correlated phalangeal quantitative ultrasound (QUS) and fracture history in children and adolescents with bone disorders and evaluated the ability of QUS to recognize fractured patients., Methods: Amplitude-dependent speed of sound (AD-SoS) and bone transmission time (BTT) were measured in 1,719 pediatric patients with bone disorders and related to fracture history. The patients were classified as (1) spontaneously (77), (2) minimal trauma (101), or (3) appropriate trauma fractured (206), and (4) nonfractured (1,335). The likelihood of fracture according to QUS was calculated as odds ratio per SD decrease (OR/SD), and the effectiveness in discriminating fractured patients was evaluated by receiver operating characteristic (ROC) analysis. The influence of age, sex, puberty, height, and BMI was explored by respective adjustments and multiple logistic regression., Results: Fractured patients showed significantly reduced AD-SoS and BTT standard deviation score (-0.32 ± 1.54 and -0.78 ± 1.49) compared to nonfractured subjects (0.43 ± 1.63 and -0.11 ± 1.34). QUS measurements paralleled the causative trauma severity, ranging from the lowest values in spontaneously fractured patients to normal values in appropriate trauma fractured subjects. The OR/SD were increasingly higher in appropriate trauma fractured, minimal trauma fractured, and spontaneously fractured patients. At ROC analysis, both parameters proved to have significant discrimination power in recognizing spontaneously and minimal trauma-fractured patients., Conclusions: QUS identifies fractured pediatric patients with bone disorders, reflecting the severity of the causative trauma with a high discrimination power for fragility fractures.

Unlabelled: This study assessed whether osteoporosis diagnosis and treatment after an osteoporotic fracture can be increased by providing osteoporosis reading material to patients and family doctors or by watching a videocassette about osteoporosis. Educating patients about osteoporosis had little impact on whether a woman received an osteoporosis diagnosis or treatment., Introduction: The purpose of this study was to investigate the impact of two education-based interventions on osteoporosis diagnosis and treatment in women ≥ 50 years of age after fragility fracture., Methods: Six to eight months after fracture, women were randomized into three groups: (1) control, (2) written materials, or (3) videocassette and written materials. Written materials for both the patient and physician detailed osteoporosis, fragility fracture, and available treatments; written materials for physicians were provided through patients. The educational videocassette presented similar information as the written material, but in greater depth. Rates of osteoporosis diagnosis and treatment following intervention were compared among groups using survival analysis methods. Statistical significance was set at p < 0.0167., Results: At randomization, 1,174 women were without osteoporosis diagnosis and treatment, and after follow-up, 12% of the control group, 15% of the written materials group (p = 0.073), and 16% (p = 0.036) of the videocassette and written materials group were diagnosed with osteoporosis (statistical comparisons to control). Treatment rates were 8% for the control group, 12% for the written materials group (p = 0.052), and 11% for the videocassette and written materials group (p = 0.157). At randomization, 1,314 women were without treatment and after follow-up therapy was initiated in 10% of the control group, 13% of the written materials group (p = 0.107), and 13% of the videocassette and written materials group (p = 0.238)., Conclusions: The educational interventions assessed in this trial were not satisfactory to increase osteoporosis diagnosis or treatment in recently fractured women to a clinically meaningful degree.

Unlabelled: Non-traumatic fractures at typical osteoporotic sites are associated with increased mortality across all age groups, particularly in men. Furthermore, in certain age subgroups of women and men, this rate remained elevated beyond 5 years for fractures of the hip, vertebrae, humerus, and other sites., Introduction: Increased mortality rates have been documented following non-traumatic hip, vertebral, and shoulder fractures. However, data are lacking as to the duration of excess mortality and whether there is increased mortality following fractures at other sites. We determined mortality up to 15 years following incident fractures at typical osteoporotic sites., Methods: Using healthcare databases for the Province of Manitoba, Canada, we identified individuals 50 years and older with an incident non-traumatic fracture between 1986 and 2007. Each fracture case was matched to three fracture-free controls. Generalized linear models were used to test for trends in mortality and to estimate the relative risk for cases after adjusting for co-morbidity and living arrangements., Results: During the study period, we identified 21,067 incident fractures in men followed by 10,724 (50.1%) deaths and 49,197 incident fractures in women followed by 22,018 deaths (44.8%). Seventy-six percent of the fractures were at sites other than the hip and vertebrae. After adjustment for age, number of co-morbidities, and level of dependence in living arrangements, the risk of death in cases, relative to controls, was increased in both sexes for hip, vertebral, humerus, wrist (in men only), and other fracture sites. Post-fracture mortality was higher in men than women. Relative mortality was the highest in the younger age groups across the spectrum of fracture sites., Conclusions: Fractures at typical osteoporotic sites are associated with increased mortality across all age groups, particularly in men. Better understanding of factors associated with increased post-fracture mortality should inform the development of management strategies.

An understanding of the pathophysiologic mechanisms of post-renal transplant (PRT) bone disease is of important clinical significance. Although bone disease occurs after all solid organ transplantation, the cumulative skeletal fracture rate remains high in PRT subjects while reaching a plateau with other transplantations. One major difference in the pathophysiology of PRT bone disease is, perhaps, due to persistent renal phosphorus (Pi) wasting. Novel phosphaturic agents have recently been suggested to participate in the development of bone disease in PRT subjects. However, it is unclear as of yet whether these factors alone or in conjunction with excess parathyroid hormone (PTH) secretion play a key role in the development of negative Pi balance and consequent bone disease in this population. In this review, I present a natural history of PRT hypophosphatemia and persistent renal Pi leak, provide pathophysiologic insight into these developments, and discuss the difficulty in diagnosing these phenotypes in both adult and pediatric populations.

Unlabelled: Pathologic fractures are often excluded in epidemiologic studies of osteoporosis. Using Medicare administrative data, we identified persons with vertebral and hip fractures. Among these, 48% (vertebral) and 3% (hip) of the fractures were coded as pathologic. Only 25% and 66% of persons with these pathologic fractures had evidence for malignancy., Introduction: Analyses of osteoporosis-related fractures that use administrative data often exclude pathologic fractures (ICD-9 733.1x) due to concern that these are caused by cancer. We examined "pathologic" fractures of the vertebrae and hip to evaluate their contribution to fracture incidence and assessed the evidence for a malignancy., Methods: We studied US Medicare beneficiaries age > or =65 with new fractures identified using ICD-9 diagnosis codes 733.13 (pathologic vert), 805.0, 805.2, 805.4, 805.8 (nonpathologic vert); and 733.14 (pathologic hip), 820.0, 820.2, 820.8 (nonpathologic hip). We further examined the proportion of cases with a diagnosis of a malignancy proximate to the fracture., Results: We identified 44,120 individuals with a vertebral fracture and 60,354 with a hip fracture. Approximately 48% of vertebral fractures and 3% of hip fractures were coded as pathologic. For only approximately 25% of persons with a "pathologic" vertebral fracture ICD-9 code, but 66% of persons with a "pathologic" hip fracture, there was evidence of a possible cancer diagnosis., Conclusion: Among US Medicare beneficiaries, one fourth of pathologic vertebral fracture and two thirds of pathologic hip fracture cases had evidence for a malignancy. Particularly for vertebral fractures, excluding persons with pathologic fractures in epidemiologic analyses that utilize administrative claims data substantially underestimates the burden of fractures due to osteoporosis.

Capillary and cavernous haemangiomas are the most common benign soft tissue tumours of infancy. Cavernous haemangiomas have larger vascular channels and frequently exist in deep dermal tissues. Many haemangiomas require no special treatment. Development of complications such as cardiac failure, malignant change, ulceration and infection are indications for intervention. In this report we present an 11-year-old girl with a pathological fracture after a minimal trauma that might be a result of secondary regional osteoporosis due to diffuse cavernous haemangioma.

The purpose was to assess osteoporotic vertebral fractures and other spinal lesions in sagittal reformations obtained from routine multidetector computed tomography (MDCT) studies of the thorax and abdomen, to compare sagittal reformations with axial images in detecting these lesions and to investigate how frequently they were missed in the official radiology report. Routine abdominal or thoracoabdominal MDCT using a standard protocol was performed in 112 postmenopausal women. Axial images and sagittal reformations were analyzed separately by two radiologists in consensus and were compared in order to evaluate how often spinal lesions could be detected. In addition the official radiology reports were assessed to determine how many of those abnormalities were identified. Spine abnormalities were visualized in 101/112 postmenopausal women. In 27 patients osteoporotic vertebral deformities were found; 6 of these were shown in the axial images, but none of these were diagnosed in the official radiology report. Additional abnormalities included degenerative disc disease, osteoarthritis of the facet joints, scoliosis, hemangiomas and bone metastases. In only 9/101 patients spine abnormalities were mentioned in the radiology report. Sagittal reformations of standard MDCT images provide important additional information on spinal abnormalities; in particular, osteoporotic vertebral deformities are substantially better detected.

The purpose of this study was to analyse the number and types of secondary fractures, and to investigate the impact of intradiscal cement leaks for adjacent vertebral fractures. Patients with osteoporotic vertebral fractures were treated with vertebroplasty. Results were documented and prospectively followed by means of computed tomography (CT) and magnetic resonance imaging. The frequency and the types of cement leakages were analysed from multiplanar CT images and secondary fractures were characterised as follows: (1) adjacent fracture in the immediate vicinity of an augmented vertebra; (2) sandwich fracture, fracture of an untreated vertebra between two vertebrae that had been previously augmented, and (3) distant fractures not in the vicinity of augmented vertebrae. A total of 385 osteoporotic vertebral fractures were treated in 191 patients (61 men, 130 women, age 70.7 +/- 9.7 years). The overall rate of cement leaks was 55.6%, including all leaks detectable by CT. Intradiscal leaks through the upper, the lower, and both endplates occurred in 18.2%, 6.8%, and 2.6%, respectively. In 39 patients (20.4%), a total of 72 secondary fractures occurred: 30 adjacent fractures in 23 patients (12.0%) with a time to fracture of 2 months [median; 1.0/4.0 months, first/third quartile (Q1/Q3)]; 11 secondary sandwich fractures in 11 patients (5.8%) after 1.5 months (median; 0.25/7.5 months, Q1/Q3); and 31 distant fractures in 20 patients (10.5%) after 5 months (median; 2.0/8.0 months, Q1/Q3). Ten of 30 adjacent fractures occurred in the presence of pre-existing intradiscal cement leaks and 20 where there was no leakage. Six of 11 sandwich fractures occurred in the presence of intradiscal leaks (five leaks in both adjacent disc spaces, one leak in the lower disc space) and five where there was no leakage. The rate of secondary adjacent and non-adjacent fractures is quite similar and there is no specific impact of intradiscal leakages on the occurrence of adjacent secondary fractures. Adjacent fractures occur sooner than distant secondary fractures. Sandwich fractures are associated with specific biomechanical conditions, with a 37.9% fracture rate in sandwich constellations.

During the last few years, vertebroplasty has gained a wide acceptance for the treatment of painful osteoporotic vertebral body fractures and osteolytic changes. However, new guidelines with significant changes in indications and technique were published recently in Europe. Therefore, the aim of this review is to highlight recent changes in indications for vertebroplasty, patient work-up and changes in procedural technique, and to give an overview of patient outcome and possible complications. Therefore, technical details like different types of fluoroscopy, needle placement, pain management during the intervention, recommended equipment, including bone cement, and the use of venography are discussed. Postprocedural issues are noted, including the risk of minor and major complications and the expected outcome of the treated patients.

Unlabelled: BMD and clinical risk factors predict hip and other osteoporotic fractures. The combination of clinical risk factors and BMD provide higher specificity and sensitivity than either alone. INTRODUCTION AND HYPOTHESES: To develop a risk assessment tool based on clinical risk factors (CRFs) with and without BMD., Methods: Nine population-based studies were studied in which BMD and CRFs were documented at baseline. Poisson regression models were developed for hip fracture and other osteoporotic fractures, with and without hip BMD. Fracture risk was expressed as gradient of risk (GR, risk ratio/SD change in risk score)., Results: CRFs alone predicted hip fracture with a GR of 2.1/SD at the age of 50 years and decreased with age. The use of BMD alone provided a higher GR (3.7/SD), and was improved further with the combined use of CRFs and BMD (4.2/SD). For other osteoporotic fractures, the GRs were lower than for hip fracture. The GR with CRFs alone was 1.4/SD at the age of 50 years, similar to that provided by BMD (GR = 1.4/SD) and was not markedly increased by the combination (GR = 1.4/SD). The performance characteristics of clinical risk factors with and without BMD were validated in eleven independent population-based cohorts., Conclusions: The models developed provide the basis for the integrated use of validated clinical risk factors in men and women to aid in fracture risk prediction.

Unlabelled: We evaluated the characteristics of 1,142 women and men who attended Canadian osteoporosis clinics and had T-score < or = -2.0 and no prior fractures to determine the predictors of first clinical fracture. Greater age and failure to start osteoporosis drug treatment increased the risk of first clinical fracture., Introduction: Although risk factors for osteoporotic fractures are well-known, it is unclear which factors predict poor prognosis in patients with primary osteoporosis. The purpose of this study was to determine prognostic factors for first clinical fracture in patients with T-score < or = -2.0 and no previous clinical fracture., Methods: We examined prospectively collected data from 1,142 patients aged 40 and over in the Canadian Database of Osteoporosis and Osteopenia. We used prognosis methodology and performed survival analysis to determine factors that increase the risk of first clinical fracture., Results: Our inception cohort (mean age = 60.6 years, 91% females) had a cumulative fracture incidence of 5.1% (incidence rate: 2.53/100 person-years). Age and osteoporosis drug use predicted incident clinical fractures in multivariable regression analyses. The risk of first fracture increased by 3% per year. Failing to initiate osteoporosis treatment increased fracture risk by 2.4 times. In addition, low physical activity, high body mass index and low T-scores were found to predict fracture risk in certain patient subgroups using tree-structured survival analysis. These findings were robust and did not change with most sensitivity analyses., Conclusion: Age and osteoporosis drug treatment are the main prognostic predictors of first clinical fracture in patients with T-score < or = -2.0.

The objective of this study was to estimate the unit costs of non-vertebral osteoporotic fractures in five European countries based on the results of the SOTI and TROPOS clinical trials in postmenopausal osteoporotic women. The information recorded in the Case Report Forms was used. The perspective of third party payers was adopted. Hip fracture unit cost was the highest. The ranges of costs among countries was narrow for hip from 8,346 euros (Italy) to 9,907euros (France), but wider for other fractures: 890 euros (Spain) to 2,022 euros (Italy) for wrist, 1,167euros (Spain) to 3,268 euros (Italy) for pelvis, 837euros (Spain) to 2,116 euros (Italy) for sternum/clavicle, 565 euros (Spain) to 908 euros (France) for rib, 1,518 euros (Spain) to 3,651 euros (Belgium) for humerus, 1,805 euros (Spain) to 3,521 euros (Italy) for leg. The costs of those fractures should be considered when estimating the cost of osteoporosis.

Studies of the management of osteoporosis in older women who have had hip or wrist fractures have found underdiagnosis and undertreatment of the disease. Few such studies have been conducted in the United States, however, and most studies have been confined to a subset of the treatments currently available to treat osteoporosis. Mail surveys were sent to 381 women between 50 and 84 years of age who had been treated for a hip or wrist fracture at a large northeast US teaching hospital between October 1, 1998, and September 30, 2000. These surveys included questions about osteoporosis risk factors and physician treatment both before and after the index fracture. Of 381 surveys mailed, 70 were returned because of an invalid address or by a relative because a patient was deceased. Of the remaining 311 surveys, 147 completed responses were received. Fifty-two percent of respondents reported having received either a prescription or a recommendation for a nonprescription medication used to treat osteoporosis before the fracture. After fracture, 60% of subjects were advised to take any osteoporosis medication, and 42% of were advised to take a prescription medication. Of women reporting no treatment advice before fracture, 33% reported treatment after. Twenty-four percent of patients reported a change in treatment after fracture versus before. No significant differences in treatment were found according to fracture history, maternal history of fracture, or maternal history of osteoporosis. Both prescription and nonprescription treatment prevalence after fracture were lower than expected, and there was only a small change in reported treatment prevalence after fracture versus before. There was also little difference in treatment prevalence based on risk factors for osteoporosis or osteoporotic fractures. A sizeable opportunity exists for intervention to reduce the risk of osteoporotic fractures for patients who have a history of fracture.

Osteodystrophy is frequently found in children with chronic cholestatic liver disease. We herein report an end-stage case of biliary atresia that was associated with multiple bone fractures and severe growth retardation. The patient, an 8-month-old female, underwent a living-related liver transplantation and thereafter showed a dramatic improvement in growth and decrease in bone fractures. A correction of the liver function is therefore considered to be a key factor in treating osteodystrophy that is related to chronic cholestatic liver disease. It is also essential to perform liver transplantation at the most appropriate time to enhance and support the growth of these patients.

The aim of this study was to increase awareness of, and to show the variable clinical and radiological features of, subchondral insufficiency fractures of the femoral head. The clinical and radiological findings in 7 patients with subchondral insufficiency fractures of the femoral head were reviewed retrospectively. The diagnosis was confirmed histologically in 4 patients. Radiographs were performed in all patients, MRI in 5 and scintigraphy in 4 patients. Radiographs showed varying degrees of femoral head collapse in 4 patients. In the remaining 3 patients radiographs showed a normal femoral head, regional osteoporosis and focal sclerosis, respectively. Magnetic resonance imaging showed a low-signal band on T1- and T2-weighted images in the subchondral bone adjacent or parallel to the articular surface associated with bone marrow oedema. Scintigraphy showed increased uptake in the femoral head. Insufficiency fractures of the femoral head are easily overlooked or confused with avascular necrosis and, when there is significant joint destruction, osteoarthritis. Unsuspected insufficiency fracture of the femoral head can lead to significant and rapid loss of bone stock in osteoporotic patients waiting for arthroplasty for osteoarthritis. Increased awareness of this condition will hopefully lead to earlier diagnosis and a successful outcome of conservative treatment.

We examined the effect of a fracture clinic intervention in reducing previously documented undertreatment of osteoporosis (OP) in individuals with fragility fractures. Fragility fracture patients presenting to five community fracture clinics with no prior diagnosis of, or treatment for OP, and whose radiographic appearance was consistent with fragility fracture, were included. These individuals (intervention group) were informed of their OP risk, and advised to follow up with their physician for assessment. A standardized letter, intended for the physician and outlining the same was provided. Three months later, a telephone interview determined whether a physician visit had occurred, and if so, what investigation and treatment recommendations were made. These outcomes were compared with those for an equal number of age- and sex-matched fragility fracture "controls," selected from among fracture clinic attendees in the 6-9 months preceding the intervention. Logistic regression was used to examine the effect of having received the intervention on physician follow-up, bone density testing, and OP treatment recommendations. The mean age of the 278 participants (139 per group) was 66.0 years; 74% were female. Adjusting for age, sex, hospital, and perceived diagnosis of OP, those who received the intervention were more likely to follow up with a physician (adjusted OR 1.85, p=0.02) and to be recommended bone density testing (adjusted OR 5.22, p<0.0001), but were not more likely to receive an OP treatment recommendation (adjusted OR 2.07, p=0.07). It is concluded that a simple fracture clinic intervention increased follow-up and investigation, but not treatment for OP, in fragility fracture patients. Individuals recommended treatment for OP were more likely to perceive themselves as having OP and to have had a previous fragility fracture. Our findings suggest that future interventions should incorporate assessment of patients' OP health beliefs and education about risk factors for fracture, and should be coupled with physician education to achieve optimal results.

Although MR imaging has been increasingly recognized as a useful tool in the diagnosis of early rheumatoid arthritis (RA) and in the assessment of disease activity, these applications have not yet been usually included in the routine management of this condition. Our goal is to review the current role of MRI in the everyday clinical management of patients with RA. The usefulness of MRI in the evaluation of articular and para-articular changes in specific locations, mainly the craniocervical region and the temporomandibular joint, are reviewed. Clinical problems derived from local extra-articular involvement, such as tenosynovitis, "rice-bodies" bursitis, and Baker's cyst rupture, are also described. Finally, we also review the value of MRI in evaluation of some complications of RA such as tendinous rupture, osteonecrosis, stress fracture, and septic arthritis/osteomyelitis.

In a pilot experiment comparing four different modalities for inducing osteoporosis in the sheep, a combination of ovariectomy, calcium/vitamin D-restricted diet and steroid administration was found to generate the highest decrease in bone mineral density (BMD). The aim of the present study was to quantify the outcome of this triple treatment in an animal model of osteoporosis in terms of alteration in bone mass, bone structure and bone mechanics. A total of 32 sheep were divided into two equal groups. Group 1 (age 3-5 years) was used as a normal control. Group 2 (age 7-9 years) was ovariectomized, fed a calcium/vitamin D-restricted diet and injected with methylprednisolone (MP) over 7 months (22 weeks MP solution, 6 weeks MP suspension). The BMD at the distal radius and tibia was determined preoperatively and at repeated intervals bilaterally using quantitative computed tomography. Steroid blood levels were determined 4 and 24 h after selected injections. BMD was measured at L3 and L4 after 7 months. Biopsies were taken from iliac crests, vertebral bodies and femoral heads, and bone structure parameters investigated by three-dimensional micro-CT. Compressive mechanical properties of cancellous bone were determined from biopsies of vertebral bodies and femoral heads. After 7 months of osteoporosis induction the BMD of cancellous bone decreased 36 +/- 3% in the radius and 39 +/- 4% in the tibia. Steroid blood levels 24 h after injection of MP suspension were significantly higher than after injection of MP solution. Changes in structural parameters of cancellous bone from the iliac crest, lumbar spine and femoral head in group 2 indicated osteoporosis-associated changes. In group 2 there was a significant reduction in BMD of the lumbar spine and a significant reduction in stiffness and failure load in compression testing of biopsies of lumbar vertebrae. In sheep, changes in the structural parameters of bone such as trabecular number and separation during osteoporosis induction are comparable to the human situation. The sheep model presented seems to meet the criteria for an osteoporosis model for fracture treatment with respect to mechanical and morphometric bone properties.

Background: The purpose of the present study was to determine differences, if any, in bone mineral density, the risk of fracture, and clinical behavior in patients with lactose intolerance investigated by hydrogen breath test., Methods: The study population (n = 218; age, mean +/- SD, 58.2 +/- 11.5 years) consisted of 103 healthy individuals negative hydrogen breath test (Delta H2 0-20 ppm; group I), and 115 individuals with evidence of lactose intolerance according to the hydrogen breath test (Delta H2 > 20 ppm), of whom 40 individuals had test results of 20 ppm < Delta H2 < 59 ppm (group II). The remaining 75 individuals were strongly positive on the hydrogen breath test (Delta H2 > 60 ppm; group III). The entire study population was measured for bone mineral density in the nondominant forearm and in the vertebra (quantitative computed tomography [qCT]). Radiographs of the spine were studied for fractures., Results: In healthy individuals, bone mineral density in the vertebra assessed by qCT (mean +/- SD, 111.2 +/- 31 mg/cc) did not significantly differ between those with mild (qCT, mean +/- SD, 109.8 +/- 35 mg/cc) and those with severe (qCT, mean +/- SD, 107.7 +/- 36 mg/cc) lactose intolerance. Lactose-intolerant individuals had more vertebral fractures per patient when compared with those with mild lactose intolerance or controls ( P < 0.05). Considering vertebral and self-reported non-vertebral fractures, no statistically significant differences were found. In the entire group, the overall occurrences of fracture in the presence of lactose intolerance and in controls were comparable after correction for age and body mass index (BMI)., Conclusions: Individuals with lactose intolerance verified by the hydrogen breath test appear not to be at risk for accelerated bone loss. Nevertheless, a relationship between vertebral fractures and an apparent lactose intolerance cannot be excluded, as a few individuals with severe lactose intolerance had a large number of vertebral fractures.

A 39-year-old woman presented with symptoms of pain in the lumbar region and lower extremities. Physical findings included restricted movement of the lumbar spine, sacroiliac joint tenderness, positive Schober's test (10-12.5 cm), and bilaterally positive Mennel and Fabere tests. Although these symptoms and findings were suggestive of ankylosing spondylitis, osteomalacia was diagnosed with the appearance of multiple pseudofractures in her pelvic X-ray and laboratory abnormalities. All her symptoms and signs resolved in 6 months with vitamin D and calcium treatment.

Epidemiologic studies have shown a high prevalence of vertebral deformities in men without a steep increase with aging, suggesting that a substantial number of these deformities are not related to osteoporosis. To determine which vertebral deformities are likely to be osteoporotic fractures, we compared vertebral deformities and bone mineral density (BMD) in a cohort of 786 men aged 51-85 years (the MINOS study). Normal vertebral height ratios were defined in a group of 120 healthy men aged 21-50 years. We classified vertebral deformities by using the semiquantitative method described by Genant et al., which was slightly modified at the level of thoracic kyphosis (T6-T9). At that level, grade 1 wedge deformities were defined as a 25-30% decrease in anterior vertebral height and grade 2 by a 30-40% decrease. The same cutoff of 40% was used for grade 3 for all vertebrae from T4 to L4. BMD was measured with a Hologic 1500 device at the lumbar spine, hip and whole body and with an Osteometer DTX 100 device at the forearm. Z-scores were calculated in 10-year age groups. The prevalence of vertebral deformities increased significantly with age. After adjustment for age and body weight, BMD did not differ between those with and without vertebral deformities. In patients having grade 2 and 3 deformities, BMD was lower than in men having no deformities or only grade 1 deformities when adjusted for age and body weight. Using the age- and body-weight-adjusted test of linear trend for sextiles of BMD, prevalence of grade 2 and 3 vertebral deformities increased with a decrease in BMD at all the sites of measurement. Grade 1 deformities were not correlated with BMD at any site. Among 126 patients who had only grade 1 vertebral deformities, 32 deformities in 30 men were confirmed as vertebral fractures according to their morphology but their BMD did not differ from the nonfractured men. These findings were confirmed when vertebral deformities were measured by the conventional morphometric method in a subgroup of 131 men. Our data suggest that a cutoff of 30% for wedge deformities from T6 to T9 and of 25% for other deformities has a high specificity and a moderate sensitivity for identifying vertebral deformities related to low BMD in men. Grade 1 deformities are often either false positive or deformities related to nonosteoporotic disease of the spine.

Chronic back tiredness or fatigue is a common complaint of people who have a history of osteoporotic vertebral fracture. Trunk muscle endurance has not been studied in people with vertebral osteoporosis, partly due to the lack of assessment tools. We developed a measure of combined trunk and arm endurance suitable for people with vertebral osteoporosis, timed loaded standing (TLS). TLS measures the time a person can stand while holding a two-pound dumbbell in each hand with the arms at 90 degrees of shoulder flexion and the elbows extended. Intraclass correlation coefficients (ICCs) for same day inter-trial and six to ten day test-retest reliability were 0.89 (lower bound 95% confidence interval [LB 95% CI] 0.79) and 0.84 (LB 95% CI 0.68), respectively, in a sample of 21 older women with no known osteoporosis. In 127 women with vertebral fractures, the ICC for same day inter-trial reliability was 0.81 (LB 95% CI 0.75). In a sub-sample of 30 of these women with vertebral fractures, the six to ten day test-retest reliability was 0.85 (LB 95% CI 0.75). Moderately strong and statistically significant (p < or = 0.05) correlations were found between TLS and sixteen of eighteen measures of physical impairment and function. Functional reach distance, gait velocity, MOS-36 Physical Function Subscale, shoulder flexion strength, and six minute walk distance were most strongly associated with TLS time. Women with vertebral fractures who endorsed having back tiredness when standing and working with the arms in front of the body, sitting to rest because of back tiredness or pain, and planning rest periods because of back tiredness or pain had significantly lower TLS times. TLS is a simple, safe physical performance measure of combined trunk and arm endurance that demonstrates acceptable reliability (inter-trial and test- retest) and concurrent validity.

This prospective study was aimed at determining the risk factors for the development of fractures in perimenopausal women. The study group (n = 3068) was comprised of a stratified population sample of women aged between 47 and 56 years. During the follow-up period of 3.6 years, 257 (8.4%) of the women sustained a total of 295 fractures. After adjustment for covariates, the relative risk (RR) of sustaining a fracture was found to be 1.4 [95% confidence interval (CI) 1.2-1.6] for a 1 standard deviation (SD) decrease in the spinal and femoral neck bone mineral density (BMD). Women with a previous fracture history were found to have an increased risk of fracture [RR 1.7 (95% CI 1.3-2.2)] and those reporting three or more chronic illnesses exhibited a RR of 1.4 (95% CI 1.0-1.9). Women not using hormone replacement therapy (HRT) had a RR of 1.5 (95% CI 1.1-2.2) for all fracture types. When osteoporotic fractures (vertebral, hip, proximal humerus and wrist fractures; n = 98) were used as an endpoint, the independent risk factors were found to be a low BMD (RR for a 1 SD decrease in both spinal and femoral neck BMD was 1.6, 95% CI 1.3-2.0), a previous fracture history (RR 1.9, 95% CI 1.3-2.9) and nonuse of HRT (RR 2.2, 95% CI 1.3-4.0). The independent risk factors for all other fractures (n = 158) were a low BMD (RR for a 1 SD decrease in the spinal BMD was 1.4, 95% CI 1.2-1.6 and in the femoral neck BMD was 1.3, 95% CI 1.1-1.5), a previous fracture history (RR 1.6, 95% CI 1.1-2.2), smoking (RR 1.8, 95% CI 1.1-2.7) and having had three or more chronic illnesses (RR 1.6, 95% CI 1.1-2.2). Weight, height, age, menopausal status, maternal hip fracture, use of alcohol, coffee consumption or dietary calcium intake were not independently associated with the development of any particular type of fracture. We conclude that the independent risk factors for perimenopausal fractures are a low bone density, previous fracture history, nonuse of HRT, having had three or more chronic illnesses and smoking, the gradient of risk being similar for spinal and femoral neck BMD measurements in the perimenopausal population. The risk factors are slightly different for perimenopausal osteoporotic than for other types of fractures.

This prospective population-based cohort study investigated factors predicting distal forearm fracture (DFF) in perimenopausal women. The study population consisted of 11,798 women from the Kuopio Osteoporosis Risk Factor and Prevention (OSTPRE) Study in Finland. Mean baseline age of these women was 52.3 (SD 2.9) years (range 47-56 years) and 68% were postmenopausal. Three hundred and sixty-eight women (3.1%) had a validated DFF during the 5-year follow-up. Previous wrist fracture, postmenopausal state, age and nulliparity were independent predictors of DFF, while hormone replacement therapy (HRT), dairy calcium and overweight protected against it in multivariate Cox regression analysis: previous wrist fracture increased the DFF risk by 158% (p < 0.0001), menopause by 69% (p = 0.002) and age by 6% per year (p = 0.010), whereas the continuous use of HRT decreased the risk by 63% (p = 0.0001), the use of dairy calcium at 1000-1499 mg/day (vs < 500 mg/day) by 39% (p = 0.004), overweight (BMI > 25 kg/m2) by 36% (p = 0.0002) and parity by 29% (p = 0.031). Combining dichotomous low weight, low use of calcium, non-use of HRT and previous wrist fracture into a risk score gave a dose-response effect by score level: the presence (vs absence) of all four risk factors resulted in a 12-fold DFF risk. Nevertheless, the sensitivity and specificity of the score for detecting DFF remained low. It was concluded that HRT, high nutritional calcium intake and overweight protect against but a history of wrist fracture predisposes to perimenopausal distal forearm fracture. A simple risk factor inquiry would help to identify perimenopausal women at high risk of distal forearm fracture.

We validated a vertebral fracture assessment (VFA) workstation developed by our group for semiquantitative assessment of vertebral fractures in large-scale, multicenter osteoporosis drug trials. Baseline and follow-up spine radiographs (lateral views) of 50 patients who participated in a clinical trial were digitized and were archived on CD-ROM. Both original radiographs and the digitized images were independently assessed by three experienced radiologists. Prevalent fracture scores of vertebrae were rated in increments of 1 on a 4-point scale. Incident fractures were defined as any worsening of grade on follow-up films. Generally good to excellent agreement among the three readers was found between the two methods, with kappa scores (kappa) from 0.91 to 0.96 for prevalence of fractures, and from 0.80 to 0.90 for incidence of fractures. Reproducibility (intra-reader variability) of each method was comparable. For assessing prevalent fracture, kappa was from 0.87 to 0.96 using radiographs, and from 0.87 to 0.94 using VFA images. For incident fractures, the kappa was from 0.78 to 0.89 using radiographs, and from 0.82 to 0.88 using VFA images. Level-specific agreement between the two approaches was consistent. Overall, there is no difference between readings of digital images and readings of conventional radiographs. The quality of the new VFA for visualization of vertebral fracture is excellent.

In 1994 the WHO proposed guidelines for the diagnosis of osteoporosis based on measurement of bone mineral density. They have been widely used for epidemiological studies, clinical research and for treatment strategies. Despite the widespread acceptance of the diagnostic criteria, several problems remain with their use. Uncertainties concern the optimal site for assessment, thresholds for men and diagnostic inaccuracies at different sites. In addition, the development of many new technologies to assess the amount or quality of bone poses problems in placing these new tools within a diagnostic and assessment setting. This review considers the recent literature that has highlighted the strengths and weaknesses of diagnostic thresholds and their use in the assessment of fracture risk, and makes recommendations for actions to resolve these difficulties.