Bisphosphonates Maintain BMD after Sequential Teriparatide and Denosumab in Premenopausal Women with Idiopathic Osteoporosis.

CONTEXT: We previously reported that sequential teriparatide followed by denosumab substantially increases BMD in premenopausal idiopathic osteoporosis (PremenIOP). OBJECTIVE: To determine whether administration of bisphosphonates after denosumab cessation is associated with stable BMD in PremenIOP. DESIGN: Open-label extension study. PARTICIPANTS: 24 PremenIOP Teriparatide-Denosumab Study participants. INTERVENTIONS: Oral alendronate (ALN), 70mg weekly, or IV zoledronic acid (ZOL), 5mg once (patient choice), was administered 7 months (M) after final denosumab dose. OUTCOMES: BMD by DXA and serum C-telopeptide (CTX) q6M; vertebral fracture assessment (VFA) and HR-pQCT q12M. RESULTS: 24 women with PremenIOP (aged 43 ± 8 years), severely affected with low trauma adult fractures (range 0-12; 9 with vertebral fractures) and/or very low BMD, had large BMD increases on sequential teriparatide-denosumab (spine: 25 ± 9%; total hip: 11 ± 6%). During the Bisphosphonate Extension, mean BMD and CTX changes in the entire group were small and not statistically significant at 6 or 12M.Women choosing ZOL (n = 6) versus ALN (n = 18) did not differ by baseline age, BMI, fractures, BMD, or CTX. On ZOL, there were small LSBMD declines and CTX increases, particularly between 6M and 12M, while greater stability was observed on ALN.Changes in BMD and CTX did not differ by duration of denosumab (36M vs <36M) or between 20 women who remained premenopausal and 4 who transitioned into menopause. Higher pre-teriparatide CTX, likely reflecting baseline remodeling status, predicted more spine and hip bone loss. No new vertebral (clinical or VFA screening) or non-vertebral fractures occurred. CONCLUSION: BMD remained stable in women with PremenIOP who received bisphosphonates after sequential teriparatide-denosumab therapy.

Clinical characteristics of pregnancy and lactation associated osteoporosis: An online survey study.

Pregnancy and lactation associated osteoporosis is a rare and often severe osteoporosis presentation. Little information is available about etiology, clinical characteristics, risk factors and predictors of severity. Using an anonymized questionnaire, we defined clinical characteristics and potential risk factors for disease severity in PLO including primiparity, heparin exposure and celiac disease. PURPOSE: Pregnancy and lactation associated osteoporosis (PLO) is a rare form of early-onset osteoporosis in which young women present with fractures, usually multiple vertebral fractures, during late pregnancy or lactation. Little information is available about etiology, clinical characteristics, risk factors and predictors of disease severity. METHODS: PLO patients were recruited to complete an anonymized online questionnaire. Disease severity was defined as total number of fractures during or after the first pregnancy associated with a fracture(s). Analyses related disease severity to potential predictors including diseases/conditions or medication exposures. RESULTS: 177 completed surveys were received between 5/29/2018 and 1/12/2022. Average age at initial PLO fracture event was 32 ± 5 years. The majority were primiparous with singleton pregnancy and 79% fractured during lactation. Subjects reported 4.7 ± 2.7 total PLO fractures, with 48% reporting ≥ 5 fractures. Vertebral fractures, reported by 164/177 responders (93%), were the most common fracture type. Conditions and medications most commonly reported included vitamin D deficiency, amenorrhea unrelated to pregnancy, nephrolithiasis, celiac disease (CD), oral steroid use, heparin products during pregnancy and progestin only contraceptive after pregnancy. CD and heparins exposure during pregnancy were significantly related to disease severity. CONCLUSION: This is the largest study characterizing clinical features of PLO to date. The large number of participants and broad range of clinical and fracture characteristics queried has yielded novel information on the characteristics of PLO and potential risk factors for its severity, including primiparity, exposure to heparin and CD. These findings provide important preliminary data that can help target future mechanistic investigations.

Bone microstructure in proton pump inhibitor users.

OBJECTIVES: We assessed skeletal microstructure and stiffness in proton pump inhibitor (PPI) users compared to non-users with high resolution peripheral quantitative computed tomography (HRpQCT) and microfinite element analysis (µFEA) and other modalities. Relationships between PPI dose/frequency and bone parameters were evaluated. METHODS: We cross-sectionally assessed skeletal health in 601 older (≥age 65 years) adults (130 PPI users and 471 non-users) participating in a multi-ethnic population-based study of aging. RESULTS: PPI users tended to have more comorbidities and take more medications than non-users. Female PPI users (n = 100) were more likely to be non-Caucasian, shorter with higher BMI, and more likely to have diabetes, lower physical activity and be using anti-depressants and thiazide diuretics compared to non-users (n = 302). Male PPI users (n = 30) were more likely to have liver disease than non-users (n = 169). In women, historical fractures (53.0 % vs. 43.4 %, p = 0.05) and falls (38 % vs. 26.8 %, p = 0.04) tended to be more frequent in PPI users compared to non-users. Number of falls was higher in women reporting daily rather than intermittent PPI use (1.8/year vs. 1.0/year, p < 0.001). In women, there were no differences in any HRpQCT or µFEA parameter. By HRpQCT, covariate-adjusted cortical volumetric bone density (Ct.vBMD) was 4.2 % lower in male PPI users vs. non-users at the tibia (p = 0.04), but this did not result in reduced stiffness. There were no other differences by HRpQCT at the tibia or radius. CONCLUSIONS: PPI use was not associated with altered skeletal microstructure or stiffness in elderly men and women. The results do not support a relationship between PPI use and microstructure.

Celiac disease and bone.

Celiac disease (CD) is an autoimmune disorder characterized by small intestinal inflammation triggered by gluten ingestion in genetically-predisposed individuals. A frequent extra-intestinal manifestation of CD is metabolic bone disease which contributes to an increased risk of fracture. The mechanisms underlying bone disease in CD remain incompletely understood, but multiple processes have been proposed including (1) malabsorption of calcium and vitamin D leading to secondary hyperparathyroidism and increased skeletal resorption, (2) pro-inflammatory cytokines altering the osteoprotegerin and receptor activator of nuclear kappa-B ligand ratio favoring osteoclastogenesis, (3) hypogonadism, and (4) low weight and malnutrition. Most studies show reduced bone mineral density in patients with CD. Bone microarchitecture is also deteriorated leading to reduced whole bone stiffness. Many, but not all investigations, have shown an increased risk of fracture associated with CD. The main stay of therapy for CD is maintaining a gluten-free diet. Improvement in bone mineral density with adherence to a gluten-free diet has been well-established. Bone mineral density remains lower, however, compared to controls and increased fracture risk can persist. There is no consensus on the timing of dual-energy x-ray absorptiometry for bone mineral density assessment in patients with CD. Routine screening for CD in patients with osteoporosis is not recommended. Little data are available on the use or efficacy of prescription osteoporosis therapeutics in patients with CD. Studies are needed to develop standardized guidelines for screening and treatment of metabolic bone disease in patients with CD to identify those who may need early intervention with prescription osteoporosis therapy.

Celiac disease and bone

Abstract Celiac disease (CD) is an autoimmune disorder characterized by small intestinal inflammation triggered by gluten ingestion in genetically-predisposed individuals. A frequent extra-intestinal manifestation of CD is metabolic bone disease which contributes to an increased risk of fracture. The mechanisms underlying bone disease in CD remain incompletely understood, but multiple processes have been proposed including (1) malabsorption of calcium and vitamin D leading to secondary hyperparathyroidism and increased skeletal resorption, (2) pro-inflammatory cytokines altering the osteoprotegerin and receptor activator of nuclear kappa-B ligand ratio favoring osteoclastogenesis, (3) hypogonadism, and (4) low weight and malnutrition. Most studies show reduced bone mineral density in patients with CD. Bone microarchitecture is also deteriorated leading to reduced whole bone stiffness. Many, but not all investigations, have shown an increased risk of fracture associated with CD. The main stay of therapy for CD is maintaining a gluten-free diet. Improvement in bone mineral density with adherence to a gluten-free diet has been well-established. Bone mineral density remains lower, however, compared to controls and increased fracture risk can persist. There is no consensus on the timing of dual-energy x-ray absorptiometry for bone mineral density assessment in patients with CD. Routine screening for CD in patients with osteoporosis is not recommended. Little data are available on the use or efficacy of prescription osteoporosis therapeutics in patients with CD. Studies are needed to develop standardized guidelines for screening and treatment of metabolic bone disease in patients with CD to identify those who may need early intervention with prescription osteoporosis therapy. Arch Endocrinol Metab. 2022;66(5):756-64

Primary angiosarcoma of thyroid.

Mesenchymal origin of primary thyroid angiosarcomas (TAS) is extremely rare and comprises less than 1% of primary thyroid cancer worldwide. While TAS are most commonly occurring in the Alpine region, there are multiple reported cases of TAS in non-Alpine regions. Diagnosis of TAS is commonly made after thyroidectomy as cytologic diagnosis can be challenging due to paucity of cells, presence of necrosis and unawareness of the disease due to rarity. We report a case of primary TAS diagnosed by cytology in a 56-year-old man who presented with a sudden onset of left neck pain, swelling and haemoptysis. He was later noted to have suspicious nodules on both lobes of thyroid on ultrasound. Fine needle aspiration of thyroid nodules showed malignant epithelioid cells. The diagnosis of TAS was made based on positive endothelial markers such as thrombomodulin and CD31, with many pertinent negatives, including negative cytokeratins,thyroid transcription factor (TTF1), thyroglobulin, calcitonin and carcinoembryonic antigen (CEA).

Comparative assessment of patient outcomes with intraluminal or subintimal crossing of infrainguinal peripheral artery chronic total occlusions.

This study compares procedural complications and clinical outcomes between subintimal crossing versus intraluminal crossing during endovascular treatment of infrainguinal peripheral artery chronic total occlusions (CTO). We identified 1335 CTO interventions in 1001 patients from the multicenter Excellence in Peripheral Artery Disease (XLPAD) registry from January 2005 to October 2015. Outcomes included 30-day and 12-month all-cause death, non-fatal myocardial infarction or stroke, peripheral artery stent, or vessel, thrombosis (ST), need for any target limb endovascular or surgical revascularization, target limb major amputation and procedural complications. A subintimal crossing technique was necessary in 388 lesions (27% overall in 1335 lesions; 34% ( n=351) in 1023 femoropopliteal lesions, and 12% ( n=37) in 312 infrapopliteal lesions, p<0.01) with a lower procedural ( p<0.01) and technical ( p<0.01) success than the intraluminal in both femoropopliteal and infrapopliteal interventions. There were no significant differences in procedural complications, major adverse cardiac events, or clinically driven target limb revascularization at 1 year between the two groups, except a higher residual dissection rate in the subintimal crossing group than the intraluminal group in femoropopliteal target vessels ( p = 0.04).

Drug-Coated Balloons: Current Outcomes and Future Directions.

Paclitaxel-coated drug-coated balloons have significantly improved short-term and mid-term clinical outcomes in patients with symptomatic femoropopliteal peripheral artery disease. However, long-term results are awaited. Furthermore, the clinical success of drug-coated balloons in the infrapopliteal peripheral arteries has been more modest and overall similar to traditional balloon angioplasty, and remains an area of unmet clinical need. This article provides an overview of the clinical evidence for paclitaxel-coated balloons in the femoropopliteal and infrapopliteal peripheral artery distributions and future directions in this area.

A phonology-free mobile communication app.

PURPOSE: Aphasia - loss of comprehension or expression of language - is a devastating functional sequela of stroke. There are as yet no effective methods for rehabilitation of aphasia. An assistive device that allows aphasia patients to communicate and interact at speeds approaching real time is urgently needed. METHODS: Behavioral and linguistic studies of aphasia patients show that they retain normal thinking processes and most aspects of language. They lack only phonology: the ability to translate (input) and/or output sounds (or written words) such as "ta-ble" into the image of a four-legged object with a top at which one works or eats. RESULTS: We have made a phonology-free communication mobile app that may be useful for patients with aphasia and other communication disorders. Particular innovations of our app include calling Google Images as a "subroutine" to allow a near-infinite number of choices (e.g. food or clothing items) for patients without having to make countless images, and by the use of animation for words, phrases or concepts that cannot be represented by a single image. We have tested our app successfully in one patient. CONCLUSIONS: The app may be of great benefit to patients with aphasia and other communication disorders. Implications for Rehabilitation We have made a phonology-free mobile communication app. This app may facilitate communication for patients with aphasia and other communication disorders.