Secondary Causes Of Osteoporosis Research Articles

High prevalence of osteoporosis among virally suppressed older people (≥60 years) living with HIV.

Our objective was to evaluate bone mineral density (BMD) among older people living with HIV at the time of enrolment into a clinical trial in Kenya. The bictegravir/emtricitabine/tenofovir alafenamide (BFTAF) Elderly Study is a clinical trial among virally suppressed people living with HIV aged ≥60 years randomized to switch to BFTAF or continue their pre-enrolment regimen. At enrolment, dual-energy x-ray absorptiometry (DXA) of the lumbar spine, total hip, and femoral neck was performed and T-scores calculated for BMD. Osteoporosis was defined as T-score -2.5 or lower and osteopenia as T-score between -1 and -2.5. Fracture risk was calculated based on clinical risk factors (not including BMD), considering HIV as a secondary cause of osteoporosis, and the correlation between FRAX®-HIV and BMD assessed. Between February and May 2022, a total of 296 participants were enrolled. All were Black African, 147 (49.7%) were female, the median age was 64 years (range 60-77), and 280 (94.6%) were on tenofovir disoproxil fumarate. The median BMD of lumbar spine, total hip, and femoral neck was 0.87 g/cm2 (interquartile range [IQR] 0.78-0.99), 0.89 g/cm2 (IQR 0.79-1.01), and 0.75 g/cm2 (IQR 0.67-0.84), respectively, with median T-scores of -1.9 (IQR -2.8 to -0.7), -1.0 (IQR -1.9 to -0.3), and -1.5 (IQR -2.2 to -0.9), respectively. Osteoporosis and osteopenia were found in 37.5% and 47.3% of participants, respectively. Major osteoporotic fracture and hip fracture 10-year median probabilities using FRAX®-HIV were 3.4% (IQR 2.8-4.6) and 1.0% (IQR 0.7-1.3). Correlation coefficients between these FRAX®-HIV probabilities and femoral neck BMD were -0.204 for major osteoporotic fracture and -0.338 for hip fracture. The prevalence of osteoporosis is high among older people living with HIV in Kenya, where DXA is not readily available and risk calculation without BMD had low correlation with measured BMD values. Additional data are required on the impact of investment in fracture risk assessment and treatment, including population-specific risk calculators.

TSH-secreting pituitary adenomas and bone.

TSH-secreting pituitary adenoma (TSHoma) is the rarest functioning pituitary tumor, with an increasing incidence over the last decades. Diagnosis is often delayed, exposing patients to a high risk of developing chronic complications of long-standing hyperthyroidism. Although thyroid hormone excess is a recognized cause of secondary osteoporosis, very few studies have investigated skeletal damage in patients with TSHoma, with data limited to bone turnover markers (BTM) and a study on the prevalence of radiological vertebral fractures (VFs) incidentally detected on chest X-ray, whereas data on bone mineral density (BMD) are anecdotal. Bone resorption is increased in TSHoma compared to controls, whereas few case reports described osteoporosis and spine fractures as early complications of TSHoma. A high prevalence of morphometric VFs was described in TSHoma compared to nonfunctioning pituitary adenoma (NFPA). Patients with fracture were older and had higher free thyroxine (fT4) levels than patients without fracture. In this specific setting, treatment with somatostatin receptor ligands seems to have a protective role on fracture risk. Based on this evidence, a comprehensive osteometabolic evaluation should be performed in all patients with TSHoma, including assessment of BTM, measurement of BMD, and morphometric evaluation of VFs, both at diagnosis and then during follow-up, particularly in patients at high risk for fragility fractures.

7686 A Case Of A 66-Year-Old Male With Systemic Macrocytosis Complicated By Osteoporosis

Abstract Disclosure: J.M. Gri: None. M. Hillhouse: None. P. madhavan: None. Background: Osteoporosis in men is underestimated and warrants investigation for secondary causes of osteoporosis. Systemic mastocytosis is a rare secondary cause of osteoporosis. Clinical Case: This is a 66-year-old male with a past medical history of severe persistent asthma, eczema, hypertension, GERD with esophagitis, basal cell carcinoma, and systemic mastocytosis (diagnosed in 2010). Family history was significant for lung cancer in both of his parents. Patient was first noted to have hyperpigmented skin lesions on his legs, trunk and upper extremities in the early 1990s. The spots were biopsied and he was diagnosed with urticaria pigmentosa in 1998. Due to persistent symptoms of facial flushing and soft stool, he was referred to Hematology and was started on antihistamines. He later underwent a bone marrow biopsy in 2010 which showed multifocal mast cell aggregates but normal trilineage hematopoiesis. He endorsed back pain shortly after his diagnosis and a DXA scan was completed. The DXA scan showed osteopenia of the spine T score of -1.8, BMD 0.999 mg/mm3 and normal bone density in bilateral hips. He had no history of fractures. He was started on alendronate and remained on the medication from 2012 to 2015. It was stopped due to intolerable symptoms of acid reflux and he required proton pump inhibitors. DXA scan in 2017 showed normal bone density of the hips and osteopenia of the lumbar spine (T score -1.2). DXA scan in 2022 showed a decrease in spine BMD by 6% (T score -1.8) from 2017 to 2022 but unchanged from 2010. Hip bone mineral density was normal but decreased by 10% since 2010 and by 6% since 2017. Labs obtained in May 2022 showed normal serum electrophoresis, normal urine calcium and creatinine ratio, calcium and vitamin D level and urine NTX of 41 nM BCE/mM (21-83) and bone specific alkaline phosphatase level of 31.5 U/L (15-41.3). After discussion with the patient, conservative management with calcium, vitamin D and exercise has been implemented along with close follow up. Should the patient’s bone turnover markers increase or fracture risk increase, additional antiresorptive therapy will be initiated. Conclusion: This case study highlights the importance of screening for osteoporosis in patients with systemic macrocytosis. As this patient was diagnosed with osteopenia at age 53, this case also emphasizes the importance of early screening in both women and men with this rare condition. Presentation: 6/3/2024

7740 Adult-Onset Hypophosphatasia Presenting As Low Alkaline Phosphatase Level Following Denosumab Use For Osteoporosis

Abstract Disclosure: J. Ocampo Mascaro: None. P. Wax: None. M. Al Mukaddam: Grant Recipient; Self; Ipsen, Incyte Research Funding. Background: Hypophosphatasia (HPP) is a genetic disease characterized by low activity of the tissue non-specific alkaline phosphatase. It has a broad range of clinical phenotypes, with adults usually presenting with an incidental low alkaline phosphatase (ALP) finding. Differentiating this from other causes of low ALP is challenging, especially when treating osteoporosis, as antiresorptive therapy such as denosumab and bisphosphonates may cause low ALP and carry the potential of increasing risk of atypical femoral fractures in patients with undiagnosed HPP. Clinical Case: A 64-year-old woman with history of nephrolithiasis, hypercalciuria, and osteoporosis (screening DXA lowest T-score -3.3 in femoral neck (FN)) but no prior fractures or dental issues was seen in clinic. Initial bloodwork showed normal range calcium, 25-OH vitamin D, and intact PTH. Pre-treatment ALP was 42 IU/L (N 39-117). Work up for secondary causes of osteoporosis was negative. Three yearly doses of IV zoledronic acid resulted in +4.2% BMD increase in lumbar spine (LS) but no changes in FN. She had no side effects but was found to have a decrease in ALP to 33 IU/L. This normalized back to 42 IU/L during a three-year drug holiday. Follow up DXA noted significant decline in BMD, hence denosumab was initiated. ALP decreased back to the 30-35 IU/L range. Fasting Vitamin B6 level (off B6 supplements for 1 week) was 23.4 ng/ml (N 2.1-21). Urine phosphoethanolamine was mildly elevated at 5 mmol/mol creatinine (N ≤4). Genetic testing evidenced a pathogenic ALPL variant (Exon 6, c.575T>C (p.Met192Thr), heterozygous) compatible with HPP. She had tolerated three doses of denosumab by then with BMD improvement of 5.0% in LS but no changes in FN and no atypical femoral fracture. Denosumab was stopped. Abaloparatide was started for osteoporosis with close monitoring for worsening hypercalciuria. Conclusion: This case demonstrates that adult HPP patients may present with subtle findings and lower range of normal ALP and may tolerate short courses of antiresorptive agents. There is a need for better screening and diagnostic criteria for adult HPP patients whose ALP levels may not be initially low before initiating antiresorptive drugs for osteoporosis. The risk of adverse effects from therapy will likely vary significantly based on the clinical severity/presentation of HPP as some adults with lower ALP ranges might be more susceptible to developing atypical femur fractures (1). Balancing atypical femur fracture risk with the benefits of antiresorptive treatment in decreasing risk of osteoporotic fractures highlights the need for better risk stratification to prevent undertreatment of osteoporosis. Reference: 1. Warren AM, Ebeling PR, Grill V, Seeman E, Sztal-Mazer S. Bilateral atypical femoral fractures during denosumab therapy in a patient with adult-onset hypophosphatasia. Endocrinol Diabetes Metab Case Rep. 2021 Sep 1;2021:21-0096. Presentation: 6/2/2024

5159 Bone Disease Related To PLS3 Gene Mutation

Abstract Disclosure: S. Saberi: None. N. Esfandiari: None. Background: A variety of genes play a role in the development of osteoporosis. One of these is PLS3, located on the X chromosome. PLS3 gene mutation leads to defective function of the protein Plastin 3. Plastin 3 functions in the binding and bundling of F-actin, a main component of the actin cytoskeleton. In the skeletal system the actin cytoskeleton regulates adaption to gravity and mechanical stress. Dysregulation of this gene is associated with diseases of the bone, including osteoporosis. Clinical Case: A 60-year-old man with a history of hearing loss since age 52, hypothyroidism diagnosed at age 57 presents to the Genetics Clinic after 2 grandsons were diagnosed with osteogenesis imperfecta. The mothers (his two daughters) of the two grandsons were found to be carriers of the PLS3 gene mutation. Because of their carrier status the patient was screened and a pathogenic partial gene deletion of exons 8 to 16 in the PLS3 gene was detected. The patient has a history of a right wrist fracture at age 16 in a fall from 8 feet height from a ladder, right leg fracture at age 45 when his leg got caught and twisted in a ladder rung, 5 rib fractures and shoulder fracture at age 53 in a fall from 3 feet into a utility hole. A DXA scan showed osteopenia in his left femoral neck (T-score -1.3), normal bone density in his total hip (T score -0.1) and lumbar spine (L1-L4 T-score -0.4). FRAX score for major osteoporotic fracture was 9.4% and hip fracture was 1.2%. Labs for secondary causes of osteoporosis were normal. Due to his gene mutation and fracture history a bisphosphonate was recommended.Clinical Lessons:Obtaining a thorough family history in people with fractures can determine the need for screening for gene mutations associated with osteoporosis. This can identify patients who need more aggressive management. Presentation: 6/2/2024

7077 A Rare Case Of Hypophosphatasia Presenting With Osteoporosis In A Young Female Patient- Diagnostic Delay In Hypophosphatasia

Abstract Disclosure: R. Abdelmasih: None. I. Ali: None. Introduction: Hypophosphatasia is a rare hereditary cause of secondary osteoporosis that affects 1/100.000 individuals. The rate of osteoporosis due to hypophosphatasia is probably underestimated as it likely goes undiagnosed in heterogeneous or milder cases. We present a case of Hypophosphatasia that presented initially with osteoporosis and went misdiagnosed for years with intermittent treatment of Bisphosphonate, luckily with no atypical fractures that prompted different course of management for osteoporosis. Case Presentation: A 44-year-old female with a history of rheumatoid arthritis and osteoporosis diagnosed 7 years prior and treated with intermittent bisphosphonate which was discontinued due to side effects including muscle aches and bone pains, presented to our endocrinology clinic to establish care for osteoporosis. Patient denied prior fractures. She reported jaw pain that is being evaluated by otolaryngology and a dentist. Family history is negative. DEXA scan showed Z scores of -1.1, -1.8, and -2.2 of the lumbar spine, femoral neck, and total femur respectively. Laboratory workup showed consistently low alkaline phosphatase (ALP) 25, 20, <20 U/L (ref range 34-123), elevated Vitamin B6 of 167 nmol/L (ref range 20-125), normal parathormone, calcium, phosphate, Vit D, magnesium, and liver enzymes. Genetic testing was sent for Tissue non-specific alkaline phosphatase (TNALP). Hypophosphatasia was diagnosed based on clinical and laboratory findings, patient was started on Asfotase alfa. Clinical course is to be followed. Discussion: Hypophosphatasia is a rare hereditary disorder due to mutation of (TNALP). In normal induvial, TNALP breaks down pyrophosphate to phosphate. It also plays a role in transferring Vit B6 into the tissues. Hence, clinical presentation due to impaired calcium-phosphate hemostasis is broad including musculoskeletal pain, pseudofractues, dental abscess, and neurological symptoms (due to accumulation of Vit B6). The clinical picture varies depending on the heterogenicity of ALPL mutation. Genetic testing is not mandated to establish diagnosis, clinical presentation and laboratory testing including low ALP and elevated Vit B6 are sufficient. However, genetic testing and counseling are recommended for the patient’s sake and their family members. Antiresorptive bone therapy is contraindicated due to a further decrease of bone turnover with reported cases of increased risk of atypical femur fracture, Bone density is reported to improve with enzyme replacement therapy with bone-targeting recombinant alkaline phosphatase (Asfotase Alpha), if further treatment is needed, anabolic treatment is preferred. We present this case to shed light on such a rare disease to decrease rates of underdiagnosis or delayed diagnosis in young patients presenting with osteoporosis for prompt treatment and improved quality of life of these patients. Presentation: 6/2/2024

Multifaceted profile of PTH excess-related secondary osteoporosis: customized therapy and rehabilitation approach

Many causes of secondary osteoporosis have been identified; endocrine types (such as those linked to male hypogonadism, Cushing’s syndrome, acromegaly, thyrotoxicosis, primary hyperparathyroidism, etc.) represent one of the most challenging ailments since a personalized approach of the endocrine disease is simultaneous required. We aimed to introduce the case of a senior lady who was diagnosed with secondary osteoporosis that was associated with primary hyperparathyroidism and a conservative approach was decided, from anti-osteoporosis drug and calcium lowering agents to the physical rehabilitation and lifestyle recommendations. She also presented double unilateral adrenal incidentaloma and a pituitary incidentaloma as well as a suspected ovarian cyst that she further declined to investigate. Mitigating the non-surgical management in primary hyperparathyroidism showcase (in addition to the zoledronic acid for both osteoporosis and hypercalcemia) a complex program of rehabilitation that included a diet intervention in terms of an adequate hydration and a personalized nutrition for kidney stones primary and secondary prevention, mild physical exercise, avoidance of calcium supplements and keeping a daily chole-calciferol replacement.

Treating Osteoporosis in Patients with Atypical Femoral Fracture.

Patients who have suffered an atypical femoral fracture while on bisphosphonates or denosumab may continue to be at risk for typical osteoporotic fractures. There are no studies to provide guidance on safe treatment for such patients. Instead, using an illustrative case, 5 principles of management are provided that may lead to decreased osteoporotic fracture risk. The first principle is to discontinue the anti-resorptive medications, which may be challenging in the patient on denosumab because of rebound vertebral fractures reported in patients stopping denosumab. The second principle is to maximize non-pharmacologic management to reduce falls and fractures. Home safety, other methods of fall risk reduction, adequate nutrition, and an exercise prescription should help reduce fracture risk. Investigating potential secondary causes of osteoporosis, particularly if the original workup was not comprehensive, is the third principle because treatment of some specific causes may lower fracture risk. Reviewing the medication list is the fourth principle, with the goal of eliminating drugs that may increase fracture risk; and considering thiazides for some patients, which may lower fracture risk. Finally, some patients may benefit from anabolic therapy. One potential (but not FDA-approved) method is to use long-term cyclic teriparatide or abaloparatide on a three-months on, three-months off schedule. Tailoring the approach to each patient is important, based on the five clinical principles, in the absence of evidence-based management recommendations.

CUL1 exacerbates glucocorticoid-induced osteoporosis by enhancing ASAP1 ubiquitination.

Glucocorticoid-induced osteoporosis is a leading secondary cause of osteoporosis. Cullin-1 (CUL1) levels are abnormally elevated in patients with osteoporosis, but the underlying mechanism remains unclear. The purpose of this study was to elucidate the mechanism of action of CUL1 in a glucocorticoid (dexamethasone, Dex)-induced osteoporosis model. C57BL/6J mice were intraperitoneally injected with Dex to establish an osteoporosis model. Mouse femur bone injury and bone formation were detected using hematoxylin-eosin or Masson staining. Apoptosis and cell cycle distribution were determined by flow cytometry. Alkaline phosphatase (ALP) activity and calcified nodules were monitored using ALP and Alizarin Red S staining. The molecular mechanism was validated by co-immunoprecipitation (Co-IP) and ubiquitination assays. CUL1 expression was enhanced in the Dex-induced osteoporosis mouse model. CUL1 silencing moderated the Dex-induced cell proliferation and osteogenesis inhibition. Moreover, CUL1 promoted the ubiquitination and degradation of ASAP1 via the SKP1-CUL1-F-box (SCF)-FBXW7 complex. CUL1 induced apoptosis and repressed osteogenesis by ASAP1. CUL1 silencing alleviated the Dex-induced osteoporosis in mice. CUL1 suppressed osteoblast proliferation and osteogenesis by promoting ASAP1 ubiquitination via the SCF-FBXW7 complex in glucocorticoid-induced osteoporosis.

Ukrainian guidelines for the prevention and treatment of glucocorticoid-induced osteoporosis

Introduction. Glucocorticoid-induced osteoporosis (GIOP) is a bone metabolic disease that develops as a result of glucocorticoid (GC) use, is one of the most frequent causes of secondary osteoporosis, leads to an increase in the risk of low-energy fractures, disability and mortality of GC users. Despite the few stu­dies conducted in Ukraine on the epidemiology and treatment of GIOP, there have been no national recommendations for its ma­nagement until now, which has become the background for their creation. The purpose was to develop national guidelines for the diagnosis, prevention, and treatment of GIOP based on the analytical analysis of modern literary sources to improve the awareness of the medical community of Ukraine, improve management, and reduce the socio-economic burden of the disease. Materials and ­methods. A group of 18 experts, leading Ukrainian scientists in various fields, was created to develop the guideline. An analysis of current literary sources on epidemiology, risk factors, diagnosis, prevention and treatment of GIOP, and monitoring of the effectiveness and safety of its treatment was carried out. Evidence was synthesized ­using the GRADE system, and a critical assessment of the quality of the recommendations was carried out using the AGREE II tool. ­Results. The guideline consists of 12 provisions on screening, diagnosis, prevention, and treatment of GIOP. The authors emphasized the need to increase the awareness of the medical community of Ukraine regarding the problem, as well as patients regarding the possible side effects of GC. They presented the features of the clinical assessment of the osteoporotic fracture risk in GC users, as well as modern and available in Ukraine methods of diagnosis and treatment of GIOP. Conclusion. The first Ukrainian guideline for screening, diagnosis, prevention, and treatment of GIOP is an important national tool for its management, which is recommended by the Board of the Ukrainian Association of Osteoporosis for use in practical health care by doctors of various specialties.

Update on Atypical Femoral Fractures.

➤ Atypical femoral fractures (AFFs) are stress fractures between the lesser trochanter and the metaphyseal flare that are most commonly related to prolonged (3 to 5 years) antiresorptive medication use.➤ An important finding is a visible transverse line in the lateral cortex, known as the "dreaded black line." Complete fractures are transverse and have minimal comminution.➤ Prodromal symptoms including hip, groin, thigh, and knee pain are present in more than one-half of cases and are usually misdiagnosed.➤ Nonoperative treatment for all patients with AFF includes withdrawal of bisphosphonates, assessment for secondary causes of osteoporosis, and optimization of vitamin D and calcium.➤ Incomplete fractures without a visible line can initially be treated nonoperatively with protected weight-bearing.➤ Intramedullary nailing is indicated for complete fractures and incomplete fractures with a visible fracture line. Delayed healing after fixation should be anticipated.➤ Treatment with parathyroid hormone (PTH) analogs (teriparatide and abaloparatide) after AFF prevents other fractures in high-risk patients, but the effect on healing of the fracture is unclear.

The Value of Mandibular Indices on Cone Beam Computed Tomography in Secondary Causes of Low Bone Mass.

Background: As implant treatment cases increase, many cases of failure/side effects also occur. Generally, dental clinics determine the density of the jawbone using cone beam CT (CBCT). Considering the known potential role of this tool for bone assessment in primary osteoporosis, this study evaluated patients with secondary endocrine causes of low bone mass. Methods: The study included 83 patients with endocrine causes of osteoporosis who were evaluated by dual-energy X-ray absorptiometry (DXA), trabecular bone score (TBS), and mental foramen (MF) region CBCT. The following CBCT indices were measured: anterior (A)-thickness of inferior mandibular cortex 10 mm anterior from MF; molar (M)-thickness of inferior mandibular cortex 10 mm posterior from MF; posterior (P)-thickness of inferior mandibular cortex 25 mm posterior from MF; symphysis (S)-thickness of inferior mandibular cortex equidistant from the centers of right and left MF. Results: The highest correlation coefficient in the secondary causes group was between the A index and the lumbar BMD (r = 0.375, p = 0.001) and the P index and the femoral neck BMD (r = 0.38, p = 0.001). Hypercortisolism seems to be the most predictable cause of secondary osteoporosis using the A, M, and P indices. The A, M, and P indices showed predictive values of the bone micro-architecture that was evaluated using TBS score, and were statistically significant. The symphysis index does not significantly predict osteoporosis or impaired bone micro-architecture. Conclusions: These findings support the potential usefulness of A, M, and P CBCT-derived radiomorphometric mandibular indices in secondary osteoporosis, underlining the well-known effects of these pathologies on bone micro-architecture rather than bone quantity.

Multiple pathological fractures with a hidden aetiology

Bone disease is a well-recognised complication of primary hyperparathyroidism (PHPT). With early diagnosis of PHPT, florid bony changes such as brown tumours, lytic lesions and pathological fractures are rarely seen now. Here, we report an unusual presentation of PHPT in the current era. A 47-year-old lady was evaluated for multiple fragility fractures. Biochemical assessment confirmed primary hyperparathyroidism. DEXA scan showed severe osteoporosis. Left parathyroid adenoma was localised with imaging. She had multiple brown tumours. She underwent parathyroid adenoma excision and recovered after surgery with improved quality of life. Proper evaluation for secondary causes of osteoporosis is vital especially in premenopausal women. Early diagnosis and treatment of PHPT prevent disastrous complications.

Glucocorticoids disrupt longitudinal advance of cortical bone basic multicellular units in the rabbit distal tibia

Glucocorticoids (GCs) are the leading cause of secondary osteoporosis. The emerging perspective, derived primarily from 2D histological study of trabecular bone, is that GC-induced bone loss arises through the uncoupling of bone formation and resorption at the level of the basic multicellular unit (BMU), which carries out bone remodeling. Here we explore the impact of GCs on cortical bone remodeling in the rabbit model. Based upon the rapid reduction of bone formation and initial elevation of resorption caused by GCs, we hypothesized that the rate of advance (longitudinal erosion rate; LER) of cortical BMUs would be increased. To test this hypothesis we divided 20 female New Zealand White rabbits into four experimental groups: ovariohysterectomy (OVH), glucocorticoid (GC), OVH + GC and SHAM controls (n = 5 animals each). Ten weeks post-surgery (OVH or sham), and two weeks after the initiation of dosing (daily subcutaneous injections of 1.5 mg/kg of methylprednisolone sodium succinate in the GC-treated groups and 1 ml of saline for the others), the right tibiae were scanned in vivo using Synchrotron Radiation (SR) in-line phase contrast micro-CT at the Canadian Light Source. After an additional 2 weeks of dosing, the rabbits were euthanized and ex vivo images were collected using desktop micro-CT. The datasets were co-registered in 3D and LER was calculated as the distance traversed by BMU cutting-cones in the 14-day interval between scans. Counter to our hypothesis, LER was greatly reduced in GC-treated rabbits. Mean LER was lower in GC (4.27 μm/d; p < 0.001) and OVH + GC (4.19 μm/d; p < 0.001), while similar in OVH (40.13 μm/d; p = 0.990), compared to SHAM (40.44 μm/d). This approximately 90 % reduction in LER with GCs was also associated with an overall disruption of BMU progression, with radial expansion of the remodeling space occurring in all directions. This unexpected outcome suggests that GCs do not simply uncouple formation and resorption within cortical BMUs and highlights the value of the time-lapsed 4D approach employed.

The Severity of Bone Loss in Cushing’s Diseases

&amp;lt;i&amp;gt;Introduction: &amp;lt;/i&amp;gt;Endogenous Cushing&amp;apos;s syndrome (CS) is a known cause of secondary osteoporosis, characterized by a loss of bone mass and density. Cushing&amp;apos;s osteopathy is one of it’s most severe complications. Abnormal bone turnover, decreased bone mineral density (BMD), and increased fracture risk are common effects of glucocorticoid excess. &amp;lt;i&amp;gt;Objectives:&amp;lt;/i&amp;gt; The aim of our work is to determine the bone densitometric profile of patients followed for Cushing&amp;apos;s disease, to define the characteristics of osteoporosis and osteopenia in these patients, and to analyze the factors influencing BMD. &amp;lt;i&amp;gt;Materials and methods: &amp;lt;/i&amp;gt;This is a retrospective descriptive study involving patients followed for Cushing&amp;apos;s disease in the endocrinology-diabetology department of the public hospital establishment (EPH) of Bologhine-Algiers, during a period of 10 years, going from the January 2013 to January 2023. &amp;lt;i&amp;gt;Results: &amp;lt;/i&amp;gt;58 patients were followed during this period with an average age was 34 years, with a clear female predominance and a sex ratio of ≈ 4. Average Z score was (-1.6) at the vertebral level and (-1.09) at the femoral level. Osteoporosis was found in 44.8% (n = 26) patients and osteopenia in 37.9% (n = 22), while normal BMD was found in 17.24% (n = 10). Note that Z-score values were significantly lower at the lumbar spine than at the femoral neck. No significant difference in BMD was found between eumenorrheic and hypo-/amenorrheic females with Cushing&amp;apos;s disease. Our study demonstrated a significant negative correlation between morning plasma cortisol and BMD. While there is a significant positive correlation between BMD and ACTH concentration in CD patients, BMD at the lumbar spine and femoral neck also had a significant positive correlation with weight and BMI. &amp;lt;i&amp;gt;Conclusion:&amp;lt;/i&amp;gt; Early detection and management of CS are essential to reduce bone complications. BMD examinations should be performed to enable rapid recognition and intervention for osteoporosis. Lumbar bone loss occurs earlier and more extensively.

P777 Is the long-term Budesonide use have any influence on Bone Mineral Density in Inflammatory Bowel Diseases?

Abstract Background Systemic steroid use, and IBD itself, both have negative effect on bone mineral density. Budesonide is a synthetic steroid with high topical glucocorticoid activity and low systemic bioavailability. When compared to systemic steroids, the frequency of side effects of budesonide appears to be quite low, however, there is no documented report about the long term budesonide use on BMD in IBD patients. We also do not know other potential side effects of long term budesonide use. In this study, we aimed to evaluate the long term budesonide use on BMD and its’ other potential side effects, in IBD patients. Methods We retrospectively reviewed the files of the patients who had been using budesonide for ≥24 months and had DEXA measurements during the follow-up period (Budesonide group). Patients in the budesonide group were matched 1:1 with patients without a history of budesonide use, in relation to pre or post registry number of each index case under budesonide. Matching between groups has been done, in terms of gender, age, type of IBD, history of resection, concomitant medications, and comorbidities. For the exact matching, move on for the next or further next available patient, pre or post of each index case, was taken as a choice. (Control group). At the initiation and completion of budesonide treatment, DEXA scans were taken, and biochemical parameters and bone fractures were recorded. We also recorded other causes of secondary osteoporosis in patients (such as comorbidities, medications, alcohol, and cigarette use), as well as cumulative steroid doses and durations in those using conventional corticosteroids. Results A total of 104 patients were included in the study, with 52 in the budesonide group and 52 in the control group. The mean duration of budesonide use was 46.13 ± 15.4 months (range: 25-94 months), and the mean cumulative budesonide usage dose was found to be 34.9 ± 11.8 g (range: 14-64.8 g) in the budesonide group. Table 1a presents the comparison of the two groups. None of the patients in the budesonide group showed deterioration in BMD during the follow-up (Table 1b and 1c). No other prominent long term side effects, valued for the file recording, was found. Conclusion Budesonide treatment seems to be safe in consideration for maintaining long term remission in IBD. Relatively low number of patients, not considering the first two year’s follow up and dropping of the cases with earlier side effects, missed for the long-term judgement under budesonide, may explain the lacking of the other potential side effects (indicated in the literature).

The Therapeutic Potential of Two Egyptian Plant Extracts for Mitigating Dexamethasone-Induced Osteoporosis in Rats: Nrf2/HO-1 and RANK/RANKL/OPG Signals.

The prolonged use of exogenous glucocorticoids, such as dexamethasone (Dex), is the most prevalent secondary cause of osteoporosis, known as glucocorticoid-induced osteoporosis (GIO). The current study examined the preventative and synergistic effect of aqueous chicory extract (ACE) and ethanolic purslane extract (EPE) on GIO compared with Alendronate (ALN). The phytochemical contents, elemental analysis, antioxidant scavenging activity, and ACE and EPE combination index were evaluated. Rats were randomly divided into control, ACE, EPE, and ACE/EPE MIX groups (100 mg/kg orally), Dex group (received 1.5 mg Dex/kg, Sc), and four treated groups received ACE, EPE, ACE/EPE MIX, and ALN with Dex. The bone mineral density and content, bone index, growth, turnover, and oxidative stress were measured. The molecular analysis of RANK/RANKL/OPG and Nrf2/HO-1 pathways were also evaluated. Dex causes osteoporosis by increasing oxidative stress, decreasing antioxidant markers, reducing bone growth markers (OPG and OCN), and increasing bone turnover and resorption markers (NFATc1, RANKL, ACP, ALP, IL-6, and TNF-α). In contrast, ACE, EPE, and ACE/EPE MIX showed a prophylactic effect against Dex-induced osteoporosis by modulating the measured parameters and the histopathological architecture. In conclusion, ACE/EPE MIX exerts a powerful synergistic effect against GIO by a mode of action different from ALN.

HIV and fracture: Risk, assessment and intervention.

With management of comorbidity in people living with HIV (PLWH) a key component of clinical care, early loss of bone integrity and clinical fracture are recognized as important issues. This review aims to describe the epidemiology of fracture in PLWH, as well as summarizing the relative balance of factors that contribute to fracture. We also aim to describe fracture risk assessment and interventional strategies to modify the risk of fracture in this population. Data from recent meta-analyses show that PLWH have significantly more fractures than the general population, with men and injecting drug users at higher risk. Modifiable factors that contribute to fracture risk in this cohort include body mass index (BMI), drug use, concurrent medications, frailty, and hepatitis C virus infection. Relating to antiretroviral therapy, current or ever tenofovir exposure has been identified as predictive of fracture but not cumulative use, and a potentially modest protective effect of efavirenz has been observed. Fracture Risk Assessment Tool scores underestimate fracture risk in PLWH with improved accuracy when HIV is considered a cause of secondary osteoporosis and bone mineral density (BMD) included. Early consideration of risk, prompting evaluation of modifiable risk factors, frailty and falls risk with bone density imaging and prompt intervention may avert fracture in PLWH. Guidance on screening and lifestyle modification is available in international guidelines. Bisphosphonates are safe and effective in PLWH, with limited data for other agents.

Cross-Disciplinary Approach of Adrenal Tumors: Insights into Primary Aldosteronism-Related Mineral Metabolism Status and Osteoporotic Fracture Risk.

Our objective was to overview the novel aspects in the field of adrenal gland neoplasms, namely, the management of bone status with respect to primary aldosteronism (PA). In the current narrative review, a PubMed study was conducted from inception until June 2023. The inclusion criteria were: human (clinically relevant) studies of any study design (at least 10 patients per study); English papers; and the following combination of key words within the title and/or abstract: "aldosterone" AND "bone", "skeleton", "osteoporosis", "fracture", "calcium", "parathyroid", "DXA", "osteocalcin", "P1NP", "alkaline phosphatase", "bone marker", "trabecular bone score", or "FRAX". The exclusion criteria were in vitro or animal studies, reviews, and case reports/series. We screened 1027 articles and finally included 23 studies (13 of case-control type, 3 cross-sectional, 5 prospective, 1 observational cohort, and 1 retrospective study). The assessments provided in these studies were as follows: nine studies addressed Dual-Energy X-ray Absorptiometry (DXA), another study pointed out a bone microarchitecture evaluation underlying trabecular bone score (TBS), and seven studies investigated the bone turnover markers (BTMs) profile. Moreover, 14 studies followed the subjects after adrenalectomy versus medical treatment, and 21 studies addressed secondary hyperparathyroidism in PA patients. According to our study on published data during a period of almost 40 years (n = 23, N = 3965 subjects aged between 38 and 64, with a mean age 56.75, and a female-to-male ratio of 1.05), a higher PTH in PA versus controls (healthy persons or subjects with essential hypertension) is expected, secondary hyperparathyroidism being associated in almost half of the adults diagnosed with PA. Additionally, mineral metabolism anomalies in PA may include lower serum calcium and higher urinary calcium output, all these three parameters being reversible under specific therapy for PA, regardless medical or surgical. The PA subgroup with high PTH seems at higher cardiovascular risk, while unilateral rather than bilateral disease was prone to this PTH anomaly. Moreover, bone mineral density (BMD) according to central DXA might show a higher fracture risk only in certain adults, TBS being a promising alternative (with a still unknown perspective of diabetes' influence on DXA-TBS results in PA). However, an overall increased fracture prevalence in PA is described in most studies, especially with respect to the vertebral site, the fracture risk that seems correctable upon aldosterone excess remission. These data recommend PA as a cause of secondary osteoporosis, a treatable one via PA intervention. There is still an area of debate the way to address BMTs profile in PA, the case's selection toward specific bone evaluation in every day practice, and further on, the understanding of the potential genetic influence at the level of bone and mineral complications in PA patients.

Osteoporosis: Investigations and Monitoring.

Osteoporosis is characterized by microarchitectural disruption of the bone, decrease in bone mineral density, and increased skeletal fragility and risk of fracture. Osteoporosis occurs due to the decoupling of bone formation and bone resorption, with a significant increase in resorption. This review article focuses on the role of laboratory investigations in the diagnosis and monitoring of treatment in patients with osteoporosis. This review article collected literature from various databases using keywords such as 'Laboratory investigations', 'Osteoporosis', 'Diagnosis', 'Monitoring', and 'Bone turnover markers'. Laboratory investigations, including serum calcium, alkaline phosphatase, vitamin D, and parathormone, are commonly performed tests to exclude secondary causes of osteoporosis and monitor the response to therapy. The biochemical markers of bone turnover are newly emerged tests for monitoring individual patients with osteoporosis. These markers are classified as bone formation and resorption markers, measurable in both serum and urine. The use of these markers is limited by biological and analytical variability. The International Federation of Clinical Chemistry and Laboratory Medicine and the International Osteoporosis Foundation recommend serum procollagen type 1 amino-terminal propeptide as the bone formation marker and β-form of C-terminal cross-linked telopeptide of type I collagen (β-CTx-1/β-CrossLaps) as the marker of choice, using standardized procedures. However, in specific cases, such as patients with chronic renal disease, CTx-1 is replaced by the resorption marker tartrate-resistant acid phosphatase 5b, as its levels are not affected by renal excretion. Bone turnover markers have emerged as tools for the assessment of osteoporosis, using standardized procedures, and are useful in monitoring therapy and treatment compliance.