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Pregnancy- and lactation-associated osteoporosis (PLO) is a rare form of osteoporosis, of which the pathogenesis and best treatment options are unclear. In this report, we describe the case of a 34-year old woman diagnosed with severe osteoporosis and multiple vertebral fractures after her first pregnancy, who was subsequently treated with teriparatide (TPTD) and zoledronic acid (ZA). We describe the clinical features, imaging examination, and genetic analysis. Substantial improvements were observed in areal and volumetric bone mineral density (BMD), microarchitecture, and strength between 7 and 40 months postpartum as assessed by dual-energy X-ray absorptiometry at the total hip and spine and by high-resolution peripheral quantitative CT at the distal radius and tibiae. At the hip, spine, and distal radius, these improvements were mainly enabled by treatment with TPTD and ZA, while at the distal tibiae, physiological recovery and postpartum physiotherapy due to leg pain after stumbling may have played a major role. Additionally, the findings show that, despite the improvements, BMD, microarchitecture, and strength remained severely impaired in comparison with healthy age- and gender-matched controls at 40 months postpartum. Genetic analysis showed no monogenic cause for osteoporosis, and it is suggested that PLO in this woman could have a polygenic origin with possible susceptibility based on familiar occurrence of osteoporosis.

Fibrodysplasia ossificans progressiva (FOP) is a rare genetic bone disorder characterized by episodic flare-ups in connective tissue, which are frequently followed by the formation of heterotopic ossification. The absence of available plasma-soluble biomarkers for flare-ups or heterotopic bone formation poses severe challenges to the monitoring of disease activity to measure or predict disease progression. Recently, 18-fluor-sodium fluoride positron emission tomography/computed tomography ([18F]NaF PET/CT) was introduced as a potential marker for ossifying FOP activity. This review discusses the pharmacokinetics of [18F]NaF in relation to the pathophysiology of FOP, and its use as a marker of local bone metabolism in a variety of bone-related disorders. In addition, the review specifically addresses the applicability of [18F]NaF PET/CT imaging in FOP as a monitoring modality.

BackgroundAssessing the extent of lung involvement is important for the triage and care of COVID‐19 pneumonia. We sought to determine the utility of point‐of‐care ultrasound (POCUS) for characterizing lung involvement and, thereby, clinical risk determination in COVID‐19 pneumonia. MethodsThis multicenter, prospective, observational study included patients with COVID‐19 who received 12‐zone lung ultrasound and chest computed tomography (CT) scanning in the emergency department (ED). We defined lung disease severity using the lung ultrasound score (LUS) and chest CT severity score (CTSS). We assessed the association between the LUS and poor outcome (ICU admission or 30‐day all‐cause mortality). We also assessed the association between the LUS and hospital length of stay. We examined the ability of the LUS to differentiate between disease severity groups. Lastly, we estimated the correlation between the LUS and CTSS and the interrater agreement for the LUS. We handled missing data by multiple imputation with chained equations and predictive mean matching. ResultsWe included 114 patients treated between March 19, 2020, and May 4, 2020. An LUS ≥12 was associated with a poor outcome within 30 days (hazard ratio [HR], 5.59; 95% confidence interval [CI], 1.26–24.80; P= 0.02). Admission duration was shorter in patients with an LUS <12 (adjusted HR, 2.24; 95% CI, 1.47–3.40; P< 0.001). Mean LUS differed between disease severity groups: no admission, 6.3 (standard deviation [SD], 4.4); hospital/ward, 13.1 (SD, 6.4); and ICU, 18.0 (SD, 5.0). The LUS was able to discriminate between ED discharge and hospital admission excellently, with an area under the curve of 0.83 (95% CI, 0.75–0.91). Interrater agreement for the LUS was strong: κ = 0.88 (95% CI, 0.77–0.95). Correlation between the LUS and CTSS was strong: κ = 0.60 (95% CI, 0.48–0.71). ConclusionsWe showed that baseline lung ultrasound ‐ is associated with poor outcomes, admission duration, and disease severity. The LUS also correlates well with CTSS. Point‐of‐care lung ultrasound may aid the risk stratification and triage of patients with COVID‐19 at the ED.

Background Osteogenesis imperfecta (OI) is a clinically heterogeneous disease characterized by extreme skeletal fragility. It is caused by mutations in genes frequently affecting collagen biosynthesis. Mutations in CREB3L1 encoding the ER stress transducer OASIS are very rare and are only reported in pediatric patients. We report a large family with a novel CREB3L1 mutation, with severe adult clinical presentation. Methods Clinical examination was performed on the family members. Next generation sequencing was performed for the causative genes for OI. The mutation was confirmed in other family members with Sanger sequencing. Results A novel homozygous mutation in CREB3L1 was identified in the three affected patients. The parents and siblings who carry the mutation in heterozygous state were clinically unaffected. The three affected siblings, who were reported to have been born healthy, presented very severe progressive skeletal malformations and joint contractures but absence of common OI characteristics including blue sclerae, deafness, and dentinogenesis imperfecta. Resorption of a part of the humerus presumably associated with fracture nonunion and pseudarthrosis. Conclusion We report a novel homozygous CREB3L1 mutation in a large Indonesian family; the homozygous affected members have survived to adulthood and they present a more severe phenotype than previously reported, expanding the clinical spectrum of OI for this gene. Osteogenesis imperfecta is characterized by high bone fragility; mutations in the OI causative gene CREB3L1 are very rare and are previously reported only in three families. Homozygous mutations in the first two families led to perinatal lethal OI whereas in the third family the pediatric patient showed severe OI. We present a novel CREB3L1 mutation in a large Indonesian OI family in which the three homozygous patients have survived into adulthood despite the severe progressive nature of the disease.

Using [18F] Sodium Fuoride (NaF) Positron Emission Tomography (PET) it is not only possible to identify the ossifying potency of a flare‐up, but also to identify an asymptomatic chronic stage of fibrodysplasia ossificans progressiva (FOP). The purpose of this study was to investigate the diagnostic role of a more widely available imaging modality, Magnetic Resonance Imaging (MRI), which is of special interest for studies in pediatric FOP patients. MRI and [18F]NaF PET/CT images at time of inclusion and subsequent follow‐up CT scans of 4 patients were analyzed retrospectively. Presence, location, and intensity of edema identified by MRI were compared with activity on [18F]NaF PET. Occurrence or progression of heterotopic ossification (HO) was examined on the follow‐up CT images. Thirteen different lesions in various muscle groups were identified: five lesions with only edema, five lesions with both edema and increased [18F]NaF uptake, one lesion with only increased [18F]NaF uptake, and two lesions with neither edema nor uptake of [18F]NaF. Mild edema, found in three lesions, was present at asymptomatic sites, which did not show increased [18F] NaF uptake or progression of HO on consecutive CT images. Moderate edema was found in three symptomatic lesions, with increased [18F]NaF on PET and progression of HO on CT. Severe edema was identified in four lesions. Interestingly, two of these lesions did not develop HO during follow‐up; one of these two even gave obvious symptoms of a flare‐up. MRI can identify whether symptoms are the result of an acute flare‐up by the presence of moderate to severe edema. The occurrence of severe edema on MRI was not always related to an ossifying lesion. The additional diagnostic value of MRI requires further investigation, but MRI does not seem to fully replace the diagnostic characteristics of [18F]NaF PET/CT in FOP. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

It is challenging to study heterotopic ossification (HO) in patients with fibrodysplasia ossificans progressiva (FOP) due to the contraindication of invasive techniques ( i.e. , bone biopsies), which can trigger flare-ups. The aim of this case study was to assess mature HO at the microarchitectural level non-invasively with high-resolution peripheral quantitative computed tomography (HR-pQCT). Depending on the patient’s mobility, HR-pQCT scans were acquired of peripherally located HO and standard distal radius and tibia regions in two FOP patients, a 33-year-old woman and a 23-year-old man, with the classical mutation (p.R206H). HO was located around the halluces, the ankles, and in the Achilles tendon. Standard HR-pQCT analyses were performed of the distal radius, tibia, and HO to quantify bone mineral density (BMD) and bone microarchitecture. Micro-finite element analysis was used to estimate failure load (FL). The outcomes were compared between HO and neighboring skeletal bone and with an age- and gender-matched normative dataset from literature. The bone parameters of the radius were within the interquartile range (IQR) of normative data. In contrast, in the tibiae of both patients, total and trabecular BMD were below the IQR, as were trabecular bone volume fraction, number, and thickness, cortical thickness, and FL. Trabecular separation and heterogeneity were above the IQR. Isolated HO in the Achilles tendon had a lower total, trabecular, and cortical BMD, trabecular bone volume fraction, and cortical thickness than the normative tibia data. Trabecular microarchitecture was within the IQR, and FL was approximately 10% higher than that of the neighboring tibia after accounting for areal differences. Other scanned HO could only be qualitatively assessed, which revealed coalescence with the neighboring skeletal bone, development of a neo-cortex, and partial replacement of the original skeletal cortex with trabeculae. To conclude, isolated HO seemed microarchitecturally more comparable to reference tibia data than the peripheral skeleton of the FOP patients. HO and skeleton also appear to be able to become one entity when contiguous.

Purpose This study aimed to illustrate the possibility of an unfavorable response to treatment with the anabolic agent romosozumab for patients with severe osteoporosis and to discuss explanations for treatment failure. Methods Dual-energy x-ray absorptiometry (DXA) including vertebral fracture assessment (VFA) and X-rays of the thoracolumbar spine was used to assess bone mineral density (BMD) and the presence of vertebral fractures before and after treatment with romosozumab. Results Our patient developed a decrease in the BMD of the hip, two incident new vertebral fractures, and worsening of one prevalent vertebral fracture during 1 year treatment with romosozumab. We have not detected non-adherence, there was no pretreatment with anti-resorptives, and we observed no signs of secondary osteoporosis and/or comorbidities. Conclusion As the number of patients treated with romosozumab is rising, it becomes more likely that more patients will be found with new fractures and/or an unfavorable BMD response. Probably, the unfavorable response is a (bad) chance finding, but we think it is crucial for clinicians and patients to exclude nonadherence, new comorbidities and pretreatment with anti-resorptives as explanation in these patients.

Eagle syndrome is a bone disease where elongation of the styloid process leads to throat and neck pain, and in severe cases neurovascular symptoms such as syncope and neuralgia. The pathophysiology of Eagle syndrome is poorly understood with various theories having been proposed how this elongation is caused. To better understand the pathophysiology, we performed a work-up in 6 patients presenting with Eagle syndrome. Patients mainly presented with pain on turning the neck (100%), foreign body sensation (67%), tension in the neck (67%), and dysphagia (50%). The typical length of the styloid process ranges from 25 to 30 mm; however, [18F]NaF (sodium fluoride) PET/CT showed elongated styloid processes with an average length of 52.1 ± 15.6 mm (mean ± SD) with increased turnover at the base of one of the styloid processes. The removed styloid processes were further examined by histology, micro-CT, quantitative backscatter electron imaging (qBEI), Fourier transform infrared spectroscopy (FTIR), and circularly polarized light imaging. Histology revealed one case of a fractured styloid process healing through callus formation and one case of pseudarthrosis. Bone mineral density and mineralization was similar in the styloid processes when compared to cortical bone samples derived from the mandibular bone of different patients. Circular polarized light microscopy showed a collagen orientation in the styloid process comparable to the cortical bone samples with a distinct separation of collagen structure between the mineralized structure and the surrounding soft tissue with FTIR analysis demonstrating a typical composition of bone. This altogether suggests that the elongated styloid processes in Eagle syndrome are mature bone, capable of endochondral repair, possibly growing from the base of the process through endochondral ossification, rather than being a form of secondary calcification of the stylohyoid ligament as previously postulated.

Fibrodysplasia ossificans progressiva (FOP) is a rare genetic bone disorder characterized by episodic flare-ups in connective tissue, which are frequently followed by the formation of heterotopic ossification. The absence of available plasma-soluble biomarkers for flare-ups or heterotopic bone formation poses severe challenges to the monitoring of disease activity to measure or predict disease progression. Recently, 18-fluor-sodium fluoride positron emission tomography/computed tomography ([18F]NaF PET/CT) was introduced as a potential marker for ossifying FOP activity. This review discusses the pharmacokinetics of [18F]NaF in relation to the pathophysiology of FOP, and its use as a marker of local bone metabolism in a variety of bone-related disorders. In addition, the review specifically addresses the applicability of [18F]NaF PET/CT imaging in FOP as a monitoring modality.Fibrodysplasia ossificans progressiva (FOP) is a rare genetic bone disorder characterized by episodic flare-ups in connective tissue, which are frequently followed by the formation of heterotopic ossification. The absence of available plasma-soluble biomarkers for flare-ups or heterotopic bone formation poses severe challenges to the monitoring of disease activity to measure or predict disease progression. Recently, 18-fluor-sodium fluoride positron emission tomography/computed tomography ([18F]NaF PET/CT) was introduced as a potential marker for ossifying FOP activity. This review discusses the pharmacokinetics of [18F]NaF in relation to the pathophysiology of FOP, and its use as a marker of local bone metabolism in a variety of bone-related disorders. In addition, the review specifically addresses the applicability of [18F]NaF PET/CT imaging in FOP as a monitoring modality.

Fibrodysplasia ossificans progressiva (FOP) is a rare genetic bone disorder characterized by episodic flare-ups in connective tissue, which are frequently followed by the formation of heterotopic ossification. The absence of available plasma-soluble biomarkers for flare-ups or heterotopic bone formation poses severe challenges to the monitoring of disease activity to measure or predict disease progression. Recently, 18-fluor-sodium fluoride positron emission tomography/computed tomography ([[sup.18] F]NaF PET/CT) was introduced as a potential marker for ossifying FOP activity. This review discusses the pharmacokinetics of [[sup.18] F]NaF in relation to the pathophysiology of FOP, and its use as a marker of local bone metabolism in a variety of bone-related disorders. In addition, the review specifically addresses the applicability of [[sup.18] F]NaF PET/CT imaging in FOP as a monitoring modality.