Objective

To determine the characteristics of femoral condyle insufficiency fracture (FCIF) lesions and their relative associations with the risk of clinical progression.

Materials and methods

This HIPAA-compliant retrospective study was approved by our Institutional Review Board. Seventy-three patients (age range, 19-95) were included after excluding patients with post-traumatic fractures, bone marrow infarct, osteochondritis dissecans, or underlying tumor. Two board-certified musculoskeletal radiologists classified morphologic findings including lesion diameter, associated bone marrow edema pattern, and associated cartilage/meniscus damage. Electronic medical charts were evaluated for symptoms, risk factors, and longitudinal outcomes, including total knee arthroplasty (TKA). Imaging characteristics were correlated with clinical findings, and comparison of outcome groups was performed using a regression model adjusted for age.

Results

The majority of patients with FCIF were women (64.4%, 47/73), on average 10 years older than men (66.28 ± 15.86 years vs. 56.54 ± 10.39 years, p = 0.005). The most common location for FCIF was the central weight-bearing surface of the medial femoral condyle; overlying full thickness cartilage loss (75.7%, 53/70) and ipsilateral meniscal injury (94.1%, 64/68) were frequently associated. Clinical outcomes were variable, with 23.9% (11/46) requiring TKA. Cartilage WORMS score, adjacent cartilage loss, and contralateral meniscal injury, in addition to decreased knee range of motion at presentation, were significantly associated with progression to TKA (p < 0.05).

Conclusions

FCIF are frequently associated with overlying cartilage loss and ipsilateral meniscal injury. The extent of cartilage loss and meniscal damage, in addition to loss of knee range of motion at the time of presentation, are significantly associated with clinical progression.

Objective

Assess the impact of knee joint loading on meniscal extrusion in normal individuals and those with varying degrees of osteoarthritis (OA).

Methods

143 healthy volunteers and patients with OA underwent 3 T MRI of the knee under unloaded and loaded conditions. OA was graded with the Kellgren-Lawrence (KL) system. Menisci were evaluated for presence of tear. Descriptive statistics were expressed as mean ± standard deviation. Loaded and unloaded groups were compared using Student's t-test. Statistic significance was defined for all calculations as p < 0.05.

Results

The cohort included 87 women and 56 men with an average age of 53 years +/- 9.7 years. Kellgren-Lawrence grade distribution was as follows: 56 with grade 0, 46 with grade 1, 25 with grade 2, 13 with grade 3, and 3 with grade 4. 23% had medial meniscus tears and 16% had lateral meniscus tears. Differences in medial meniscal extrusion between loading and unloading were significant in the entire cohort (p < 0.0001). Statistically significant difference in medial meniscus extrusion with loading and unloading were found for KL score group of 0, 1 and 3 (p < 0.001, p < 0.001 and p = 0.005). Interestingly, no significant differences in extrusion with loading and unloading were found for the lateral meniscus (p = 0.07).

Conclusion

Our study demonstrated that medial meniscal extrusion significantly increased during loading, specifically in those low KL scores (0 and 1) and in KL score of 3. Loaded MRI may more accurately determine the extent of medial meniscal extrusion in particular in those with no to minimal OA.

Background

There is evidence that human immunodeficiency virus (HIV) infection and antiretroviral therapy (ART) are independent risk factors for osteoporosis and fracture which is not solely explained by changes in bone mineral density. Thus, we hypothesized that the assessment of trabecular microstructure might play an important role for bone quality in this population and might explain the increased fracture risk. In this study, we have assessed bone microstructure in the proximal femur using high-resolution magnetic resonance imaging (MRI) as well as in the extremities using high resolution peripheral quantitative computed tomography (HR-pQCT) in HIV-infected men and healthy controls and compared these findings to those based on areal bone mineral density (aBMD) derived from dual X-ray absorptiometry (DXA) which is the standard clinical parameter for the diagnosis of osteoporosis.

Methods

Eight HIV-infected men and 11 healthy age-matched controls were recruited and informed consent was obtained before each scan. High-resolution MRI of the proximal femur was performed using fully balanced steady state free precession (bSSFP) on a 3T system. Three volumes of interest at corresponding anatomic locations across all subjects were defined based on registrations of a common template. Four MR-based trabecular microstructural parameters were analyzed at each region: fuzzy bone volume fraction (f-BVF), trabecular number (Tb.N), thickness (Tb.Th), and spacing (Tb.Sp). In addition, the distal radius and distal tibia were imaged with HR-pQCT. Four HR-pQCT-based microstructural parameters were analyzed: trabecular bone volume fraction (BV/TV), Tb.N, Tb.Th, and Tb.Sp. Total hip and spine aBMD were determined from DXA.

Results

Microstructural bone parameters derived from MRI at the proximal femur and from HR-pQCT at the distal tibia showed significantly lower bone quality in HIV-infected patients compared to healthy controls. In contrast, DXA aBMD data showed no significant differences between HIV-infected patients and healthy controls.

Conclusions

Our results suggest that high-resolution imaging is a powerful tool to assess trabecular bone microstructure and can be used to assess bone health in HIV-infected men who show no differences to healthy males by DXA aBMD. Advances in MRI technology have made microstructural imaging at the proximal femur possible. Further studies in larger patient cohorts are clearly warranted.

Context

Idiopathic osteoporosis (IOP) affects otherwise healthy young individuals with intact gonadal function and no secondary cause of bone fragility. In premenopausal women with IOP, a low trauma fracture is evidence of impaired bone quality and strength. The extent to which low bone mineral density (BMD) by dual-energy x-ray absorptiometry (DXA) reflects low volumetric BMD, bone microstructure, and strength is uncertain in the absence of low trauma fracture.

Objective

The objective of the study was to compare three-dimensional volumetric BMD and bone stiffness in premenopausal women with IOP based on fracture history, those with idiopathic low BMD (Z score ≤ -2.0) and no low trauma fracture, and normal age-matched controls.

Design

We measured volumetric BMD and bone geometry by central quantitative computed tomography (cQCT) scans of the spine and hip and estimated bone stiffness by finite element analysis of cQCT data sets in 32 premenopausal women with IOP, 12 with idiopathic low BMD, and 34 controls.

Results

Subjects had comparable decreases in total and trabecular volumetric BMD, cortical thickness, and whole-bone stiffness compared with controls, regardless of fracture history. These differences remained significant after controlling for age, body mass index, and bone size. The positive predictive values of a DXA Z score of -2.0 or less for a cQCT volumetric BMD Z score of -2.0 or less were 95% at the lumbar spine, 90% at the total hip, and 86% at the femoral neck.

Conclusion

Women with idiopathic low BMD alone and those with low trauma fractures had comparable deficits in bone mass, structure, and stiffness. Low areal BMD by DXA is fairly accurate for predicting low volumetric BMD by cQCT. These results are consistent with three-dimensional bone imaging at the iliac crest, radius, and tibia in premenopausal IOP and suggest that the term osteoporosis may be appropriate in women with Z scores below -2.0, whether or not there is a history of fracture.

Because single-center studies have reported conflicting associations between microarchitecture and fracture prevalence, we included high-resolution peripheral quantitative computed tomography (HR-pQCT) data from five centers worldwide into a large multicenter analysis of postmenopausal women with and without fracture. Volumetric BMD (vBMD) and microarchitecture were assessed at the distal radius and tibia in 1379 white postmenopausal women (age 67 ± 8 years); 470 (34%) had at least one fracture including 349 with a major fragility fracture. Age, height, weight, and total hip T-score differed across centers and were employed as covariates in analyses. Women with fracture had higher BMI, were older, and had lower total hip T-score, but lumbar spine T-score was similar between groups. At the radius, total and trabecular vBMD and cortical thickness were significantly lower in fractured women in three out of five centers, and trabecular number in two centers. Similar results were found at the tibia. When data from five centers were combined, however, women with fracture had significantly lower total, trabecular, and cortical vBMD (2% to 7%), lower trabecular number (4% to 5%), and thinner cortices (5% to 6%) than women without fracture after adjustment for covariates. Results were similar at the radius and tibia. Similar results were observed with analysis restricted to major fragility fracture, vertebral and hip fractures, and peripheral fracture (at the radius). When focusing on osteopenic women, each SD decrease of total and trabecular vBMD was associated with a significantly increased risk of major fragility fracture (OR = 1.55 to 1.88, p < 0.01) after adjustment for covariates. Moreover, trabecular architecture modestly improved fracture discrimination beyond peripheral total vBMD. In conclusion, we observed differences by center in the magnitude of fracture/nonfracture differences at both the distal radius and tibia. However, when data were pooled across centers and the sample size increased, we observed significant and consistent deficits in vBMD and microarchitecture independent of total hip T-score in all postmenopausal white women with fracture and in the subgroup of osteopenic women, compared to women who never had a fracture. © 2016 American Society for Bone and Mineral Research.

Resistance to androgen deprivation therapy, or castration-resistant prostate cancer (CRPC), is often accompanied by metastasis and is currently the ultimate cause of prostate cancer-associated deaths in men. Recently, secondary hormonal therapies have led to an increase of neuroendocrine prostate cancer (NEPC), a highly aggressive variant of CRPC. Here, we identify that high levels of cell surface receptor Trop2 are predictive of recurrence of localized prostate cancer. Moreover, Trop2 is significantly elevated in CRPC and NEPC, drives prostate cancer growth, and induces neuroendocrine phenotype. Overexpression of Trop2 induces tumor growth and metastasis while loss of Trop2 suppresses these abilities in vivo. Trop2-driven NEPC displays a significant up-regulation of PARP1, and PARP inhibitors significantly delay tumor growth and metastatic colonization and reverse neuroendocrine features in Trop2-driven NEPC. Our findings establish Trop2 as a driver and therapeutic target for metastatic prostate cancer with neuroendocrine phenotype and suggest that high Trop2 levels could identify cancers that are sensitive to Trop2-targeting therapies and PARP1 inhibition.