Violet Fox: A Clinical View of Vertebral Fractures.

Had Violet's abdominal MR not been performed, or its findings not appreciated, the cause of her clinical event might never have been known because our current concept of osteoporotic vertebral fracture (VF) is substantially predicated on a change in either vertebral height or shape on lateral or sagittal spine imaging. The intention of this commentary is to stimulate a multidisciplinary conversation of osteoporotic VFs from an integrated clinical, physiological, and imaging perspective. For research and epidemiological purposes, osteoporotic VFs have been defined as a reduction in anterior, middle, or posterior vertebral height although the required minimum height reduction (e.g., 15% or 20%) varies among definition schemes. We further classify osteoporotic VFs to be "clinical" when they are accompanied by back pain and "morphometric" when they are not, and we have generally accepted the assertion that most of the osteoporotic VFs are painless, that is, morphometric. This dichotomous VF definition scheme has been the foundation of osteoporosis epidemiology and the primary endpoint in most pivotal osteoporosis pharmaceutical trials. Although, having served the osteoporosis community well, our clinical experience, refined by recent insights into vertebral anatomy and spinal biomechanics, advances in vertebral imaging, and 2 decades of vertebral augmentation suggest that the spectrum of osteoporotic VFs is more complicated than this scheme suggests.

An uncommon cause of acquired osteosclerosis in adults: hepatitis C-associated osteosclerosis.

Hepatitis C-associated osteosclerosis (HCAO) is a rare sclerosing bone condition characterized by debilitating, predominantly lower extremity bone pain, accelerated bone turnover, and a generalized increase in histologically normal trabecular and cortical bone tissue. Herein we report the clinical presentation and imaging results of the 19th case of HCAO. Clinicians, particularly those caring for a population at risk for HCV infection, should be aware of this uncommon condition. The etio-pathogenesis of HCAO remains obscure but may bear important lessons in bone biology that could lead to new treatment options for osteoporosis.

Radiographic findings in Waldenström's macroglobulinemia resembling fibrogenesis imperfecta ossium (FIO): a case report.

A case of Waldenström's macroglobulinemia with radiographic features of fibrogenesis imperfecta ossium is presented. The case raises the possibility that these radiographic findings might be more common in Waldenström's macroglobulinemia than previously appreciated, and illustrates the need for bone biopsy to establish a definitive diagnosis of fibrogenesis imperfecta ossium.

Mutations in NOTCH2 in families with Hajdu-Cheney syndrome.

Hajdu-Cheney syndrome (HCS) is a rare genetic disorder whose hallmark is acro-osteolysis, shortening of terminal phalanges, and generalized osteoporosis. We assembled a cohort of seven families with the condition and performed whole exome resequencing on a selected set of affected patients. One protein-coding gene, NOTCH2, carried heterozygous truncating variants in all patients and their affected family members. Our results replicate recently published studies of HCS and further support this as the causal gene for the disorder. In total, we identified five novel and one previously reported mutation, all clustered near the carboxyl terminus of the gene, suggesting an allele specific genotype-phenotype effect since other mutations in NOTCH2 have been reported to cause a form of Alagille syndrome. Notch-mediated signaling is known to play a role in bone metabolism. Our results support a potential therapeutic role for Notch pathways in treatment of osteoporosis.

Multifocal nodular periostitis associated with prolonged voriconazole therapy in a lung transplant recipient.

We report a case of painful, nodular periostitis in a lung transplant recipient on long-term voriconazole therapy. Symptoms, signs, and laboratory abnormalities resolved quickly after drug withdrawal. The presentation more closely resembles periostitis deformans than hypertrophic osteoarthropathy, suggesting that the fluoride moiety of voriconazole may be pathogenic for this condition. Clinicians should be aware of this association.

Technetium-99m-methyl diphosphonate bone scintigraphy may be helpful in preoperative planning for vertebroplasty in multiple myeloma: two cases.

Favorable vertebroplasty outcomes reflect accurate preoperative identification of vertebral fracture targets, operator proficiency, and assiduous fracture aftercare. Conventional teaching is that nuclear bone scintigraphy is not helpful in the management of osteolytic myeloma bone disease. Nuclear bone scintigraphy in two patients with multiple myeloma and vertebral fracture pain convincingly identified the fracturing vertebral level and provided confidence that synchronous vertebral fractures were not missed, whereas neither had been appreciated by either radiography or magnetic resonance imaging.

Identifying Incomplete Atypical Femoral Fractures With Single-Energy Absorptiometry: Declining Prevalence.

BACKGROUND: Atypical femur fractures (AFFs) are associated with long-term bisphosphonate (BP) therapy. Early identification of AFF prior to their completion provides an opportunity to intervene, potentially reducing morbidity associated with these fractures. Single-energy X-ray absorptiometry (SE) is an imaging method recently shown to detect incomplete AFF (iAFF) prior to fracture completion. METHODS: Between May 2013 and September 2014, we assessed 173 patients who had been prescribed BP therapy for >5 years for iAFF using SE at their presentation for routine bone mineral density testing. We compared these findings with those of our previously published prospective study (n = 257) in which the femur was imaged for iAFF using dual-energy X-ray absorptiometry. In addition, we estimated the yearly prevalence of complete AFF among patients with subtrochanteric fracture at our institution from 2006 to 2014, and we evaluated prescribing trends for BP in Ireland from 2009 to 2014. RESULTS: No patients had iAFF using SE femur compared with a prevalence of 2.7% in the earlier study. Between 2006 and 2014, we observed a rise and decline in AFFs at our hospital and a similar national trend in BP prescribing. CONCLUSIONS: AFFs appear to be decreasing. New customized scan modes of dual-energy X-ray absorptiometry systems, which visualize the entire femur at high image quality and take measurements, have the potential to identify iAFF prior to fracture completion and to ascertain those at highest risk of AFF.

Initial report of the osteogenesis imperfecta adult natural history initiative.

BACKGROUND: A better understanding of the natural history of osteogenesis imperfecta (OI) in adulthood should improve health care for patients with this rare condition. METHODS: The Osteogenesis Imperfecta Foundation established the Adult Natural History Initiative (ANHI) in 2010 to give voice to the health concerns of the adult OI community and to begin to address existing knowledge gaps for this condition. Using a web-based platform, 959 adults with self-reported OI, representing a wide range of self-reported disease severity, reported symptoms and health conditions, estimated the impact of these concerns on present and future health-related quality of life (QoL) and completed a Patient-Reported Outcomes Measurement Information System (PROMIS®) survey of health issues. RESULTS: Adults with OI report lower general physical health status (p < .0001), exhibit a higher prevalence of auditory (58% of sample versus 2-16% of normalized population) and musculoskeletal (64% of sample versus 1-3% of normalized population) concerns than the general population, but report generally similar mental health status. Musculoskeletal, auditory, pulmonary, endocrine, and gastrointestinal issues are particular future health-related QoL concerns for these adults. Numerous other statistically significant differences exist among adults with OI as well as between adults with OI and the referent PROMIS® population, but the clinical significance of these differences is uncertain. CONCLUSIONS: Adults with OI report lower general health status but are otherwise more similar to the general population than might have been expected. While reassuring, further analysis of the extensive OI-ANHI databank should help identify areas of unique clinical concern and for future research. The OI-ANHI survey experience supports an internet-based strategy for successful patient-centered outcomes research in rare disease populations.

Kyphoplasty and vertebroplasty: how good is the evidence?

The absence of Level I evidence undermines the credibility of all clinical studies pertaining to percutaneous vertebral augmentation (ie, kyphoplasty and vertebroplasty). The powerful desire to relieve suffering in the frail elderly cannot substitute for a rigorously designed randomized controlled trial comparing vertebral augmentation with continued nonoperative care. Though the level of available evidence is currently inadequate, its quality is improving.

Infected vertebroplasty: case report and review of literature.

STUDY DESIGN: Case report. OBJECTIVES: To describe a case of infected vertebroplasty and to demonstrate the importance of polymerase chain reaction (PCR) in the diagnosis of such infections. SUMMARY OF BACKGROUND DATA: Infection of the vertebroplasty site is an uncommon complication of vertebroplasty. Only 4 cases have been reported in the literature so far, and an organism could be identified in only 2 of those cases. To our knowledge, the use of PCR to diagnose infection in these cases has not been reported before. METHODS: Vertebroplasty, laminectomy, radiology, fluid aspiration, microbial culture, and 16S RNA PCR. RESULTS: A 73-year-old diabetic woman underwent vertebroplasty for L2 and L3 vertebral compression fractures followed by L4-L5 laminectomy for spinal stenosis. Three months later, she had an L1 fracture that was augmented with vertebroplasty. Six months later, she presented with incapacitating low back pain. There was a fluid-filled cavity surrounding the polymethylmethacrylate in the L1 and L2 vertebral bodies. The fluid had 95,000 white blood cells with 96% neutrophils, grew nothing on culture, but had 100% homology with Streptococcus agalactiae on 16S ribosomal nucleic acid analysis. CONCLUSIONS: We report a case of infected vertebroplasty with atypical radiologic findings of vertebral infection. To our knowledge, this is the third reported case where an organism could be isolated for these infections and the first time PCR has been used to diagnose such an infection.

Musculoskeletal manifestations of mild osteogenesis imperfecta in the adult.

The musculoskeletal manifestations of mild forms of osteogenesis imperfecta are not well defined in the adult. The aim of this study was to characterize the musculoskeletal manifestations and resulting impairments reported by adults with mild osteogenesis imperfecta. For this task a survey of musculoskeletal symptoms and impairments was hosted on the Osteogenesis Imperfecta Foundation web site for 6 weeks. Survey responses are reported herein. There were 111 unduplicated, adult respondents (78 female). Mean age was 40.8 years. More than one-quarter of 3,410 lifetime fractures occurred in adulthood. Nearly half of respondents reported an established diagnosis of "arthritis" (usually osteoarthritis), and the majority of these reported some degree of impairment attributable to arthritis. Articular pain, stiffness and instability were dominant in the large, weight-bearing joints of the lower extremities. Back pain and scoliosis were common. Of the respondents, 15% required assistance with light physical tasks and personal care. Two-thirds reported joint hyper-mobility, and one-third reported a previous tendon rupture. Complex regional pain syndrome was rare. Respondents reported frequent use of medications known to have potential adverse skeletal effects. In spite of these concerns the majority rated their overall physical health as good or excellent. Adults with mild osteogenesis imperfecta continue to sustain fractures into adulthood, and the majority reports some functional impairment due to musculoskeletal issues. Significant impairment is not rare.