Osteopenic Range Research Articles

Ageing, osteoporosis and intellectual disability; risks differ, and diagnosis can be missed

AbstractBackgroundPeople with intellectual disability often present atypically for various health conditions, making it challenging to identify concerns, particularly when communication challenges are also considered. Additionally, they may face barriers to healthcare access, resulting in many conditions going unnoticed. Health screening inequities are also evident in this population, and osteoporosis, a silent condition often only diagnosed postfracture, requires screening; however, if this does not happen, it may result in unnecessary fracture. Therefore the aim of this study is to identify predictors of osteoporosis in older adults with intellectual disability and examine potential inequity in the diagnosis of the condition.MethodsThe study used data from the Intellectual Disability Supplement to The Irish Longitudinal Study on Ageing (IDS‐TILDA). Bone quality was measured using quantitative ultrasound (QUS). Logistic regression was performed to identify significant predictors of poor bone quality, including chronic health conditions, dietary intake, medication use and activity levels.ResultsOut of 575 participants who completed QUS, osteoporosis prevalence was objectively measured at 41%, with a further 33.2% measured within the osteopenic range, but less than 2 in 10 had a doctor's diagnosis of osteoporosis. Reported Dual‐Energy X‐ray Absorptiometry screening uptake was low at 18.2%. Three major predictor variables of osteoporosis and osteopenia were found significant: difficulty walking 100 yards, taking antiepileptic drugs medicines and taking proton pump inhibitors. The model achieved an overall classification accuracy of 70.8% for osteopenia and 72.5% for identifying osteoporosis.ConclusionThe study highlights the different risk factors in people with intellectual disability, the potential for missed diagnoses and the likelihood there is inadequate screening. There is an urgent need for robust risk assessment and reasonable adjustments to ensure equitable screening and targeted preventive strategies. Clinicians must consider specific concerns for this population to avoid missed diagnoses and reduce the adverse effects of osteoporosis/osteopenia, such as an increased risk of fragility fractures.

THU455 Sclerostin Inhibitor Use In The Medical Management Of Osteogenesis Imperfecta Type III

Abstract Disclosure: M.D. Lundholm: None. A. Derkyi: None. S. Talvacchio: None. J.C. Marini: Other; Self; Ultragenyx, Amgen Inc. L.Z. Khan: None. Background: Osteogenesis imperfecta (OI) is a rare collagen-related hereditary skeletal disorder with an increased fracture risk from minimal trauma, short stature, and bone deformity. OI is associated with defects in collagen structure or synthesis, high bone turnover, and paradoxical bone hypermineralization. The optimal medical therapies for bone health in these patients are unknown. Clinical Case: A 27-year-old woman with OI presented to clinic for bone health. She was diagnosed with OI type III by phenotype, collagen biochemistry, and genetic analyses (heterozygous for a COL1A1 Gly187Ala substitution) following fractures at age 4 mos. She experienced dozens of fractures, has had orthopedic hardware in bilateral femora, left tibia, humerus, and radius, and right tibia, as well as spine fusion at age 7 yrs. She had not fractured in over 3 yrs which she attributed to the stability of her automatic wheelchair. She had no family history of OI and had been in studies at the NIH; from ages 6-9 yrs she received pamidronate (1 mg/kg/cycle q3m) with BMD improvement. Presently, her vitals were normal, with height of 3’6” (25-50th percentile for type III OI females) and weight of 64 lbs (BMI 25.5 kg/m2). On exam she had blue sclera, midface hypoplasia, dentinogenesis imperfecta, severe kyphosis and scoliosis, and a barrel chest. She had normal calcium, PTH, and 25-OH vitamin D levels. Skull CT showed 1 mm increase in basilar invagination (16 to 17 mm). DEXA demonstrated progressive decline in radial BMD from 0.671 g/cm2 to 0.625 g/cm2 over 3 yrs (z-score -0.4 to -1.1) into the osteopenic range. For worsening bone disease, she is starting romosozumab 210 mg monthly. Discussion: While several agents increase BMD in OI, there are no placebo-controlled studies to show an effect on fracture rate. Bisphosphonates including pamidronate are used most commonly, with increased areal BMD, decreased bone turnover, but also increased mineralization of already brittle bone. Overall, two Cochran reviews failed to support decreased fracture rates from bisphosphonates, and there is risk of adynamic bone with chronic use. There is even less evidence for use of denosumab which is additionally associated with a rebound effect upon discontinuation. Sclerostin inhibitors are the newest agents with both anabolic and antiresorptive effects and good results in OI mouse models. Phase 2 data with sestrusumab showed increased BMD and decreased bone turnover. Ongoing studies are looking at sclerostin inhibitor use in adults and adolescents. From a practical standpoint, romosozumab has a shorter effect with quicker offset than bisphosphonates if needed to stop for fracture healing. Conclusion: Sclerostin inhibitors are an option for the medical treatment of OI. Further investigation is needed to determine long-term safety, optimal duration, and use of sclerostin inhibitors in combination with antiresorptive agents in OI. Presentation: Thursday, June 15, 2023

FRI684 So Strong Yet So Fragile: Bilateral Periprosthetic Fractures On Denosumab

Abstract Disclosure: A. Syeda: None. F.S. Mirza: None. Background: Denosumab (DN) is a potent antiresorptive and has been associated rarely with atypical femoral fractures. We hereby report the first case of simultaneous bilateral femoral periprosthetic fractures (PPF) while on DN therapy (DNT). Clinical Case: A 78-year-old female with severe osteoporosis on DNT presented in January 2023 with bilateral femoral PPF after a mechanical fall whereby she tripped and landed on her knees. The patient had initially presented to us in late 2012. Treatment history included alendronate (ALN) for 5 years, on drug holiday since 2010. She underwent bilateral knee replacement surgeries in 2012 and DNT was started in 2013 after initial evaluation. She also had primary biliary cirrhosis, and although bone density (BD) improved on DNT, she exhibited escape from DN mediated suppression of bone resorption possibly related to the liver disease that was previously reported (1). DNT was stopped 5 years later when spine BD improved to osteopenic range and ALN 70 mg weekly was started. 1 year later, bone resorption markers were still elevated and zoledronic acid was substituted for ALN. She fell and had a pubic ramus fracture 11 months later. BD showed a 6% decrease for mean total hip and baseline forearm BD showed T-score of -3.7 on the right. DNT was restarted in December 2020 and continued every 6 months. Her health continued to deteriorate over next two years, with increase in LFTS, new anemia and thrombocytopenia due to a combination of myelodysplastic syndrome and splenomegaly. She also needed transcatheter aortic valve replacement for worsening CHF. She tripped and fell in January 2023. X-ray showed acute supracondylar bilateral PPF with comminution. She was high risk for anesthesia and anticoagulation was withheld due to a history of thrombocytopenia and gastrointestinal bleeding. Prior to the anticipated orthopaedic procedure, the patient developed severe hypotension and a rapid drop in hematocrit due to hemorrhagic shock. The family had requested DNR due to the multitude of medical issues. Conclusion: Occasional PPF have been reported in the setting of DNT, which may reflect the severity of osteoporosis. Altered stress distribution and decreased tensile strength of the bone secondary to screw/pin placement are thought to contribute to PPF, although the occurrence of PPF as an unusual presentation of an AFF cannot be excluded. Contribution of other comorbidities to poor bone quality may also have contributed to the bilateral PPF with poor outcome in our patient. 1. Vedere, T.R. and Mirza, F.S., 2017, April. Escape from Denosumab Mediated Suppression of Bone Resorption in Primary Biliary Cirrhosis. In 99th Annual Meeting of the Endocrine Society. Endocrine Society. Presentation: Friday, June 16, 2023

ODP090 Fragility Fractures and Osteoporosis Screening in Patients with Chronic Lymphocytic Leukemia

Abstract Chronic lymphocytic leukemia (CLL) and osteoporosis are diseases of older adults with high prevalence rates. CLL infiltrates the bone marrow, increasing bone resorption and demineralization which contribute to the pathophysiology of osteoporosis. Despite this, there are limited clinical data describing the association of CLL with osteoporosis and fracture risk. We hypothesized that osteoporosis and fragility fractures (FF) are common in patients with CLL. The Huntsman Cancer Institute (HCI) has a CLL database which includes all patients diagnosed with CLL since January 1, 2000 and received care at the HCI. Patients included were identified from the CLL database with ICD-9 and 10 codes associated with osteopenia, osteoporosis and/or presence of a FF. Of the 57 patients included, 67% were female (n=38) with a mean age of 69 ± 10 years and 93% Caucasian. 60% (n=34) had RAI stage of 0-1 with genetic changes noted as follows: Del(13q) 46% (n=26), Del(17p) 7% (n=4), Del(11q) 5% (n=3), and Trisomy 12 14% (n=8). IGVH mutation was present in 31.6% of patients (n=18). 47% (n=25) of patients were treated with chemotherapy, of which Rituximab (n=14), Bendamustine (n=7), Cyclophosphamide (n=5), and Ibrutinib (n=5) were the most frequently used. 58.5% (n=32) had a history of FF, with 84% occurring in the spine (n=27/32). Assessment for Vitamin D deficiency and hyperparathyroidism were performed in 54% (n=31) and 21% (n=12) of the cohort respectively. Even though every patient in the study either had a diagnosis of osteoporosis by ICD code or FF, only 44% (n=25) of patients had an available DXA scan for our review, and only 31% (n=18) received treatment for osteoporosis. Of those with a DXA, the worst T score was in the right femoral neck (T score -1.9, IQR -1.5 to -2.5) with 44% (n=14/32) either having T scores in the normal or osteopenic range. Interestingly, FF was associated with higher T scores in the spine (FF spine T score -1. 0±1.5 vs no FF T score -2.2±0.8, p=0. 03). Clinical factors associated with FF were male sex (83% men vs 46% women, p<0. 01) and positive smoking history (93% smokers vs 46% non-smokers, p<0. 01). Use of chemotherapy and hip T scores were not associated with FF. The data from our study suggests that patients with CLL are predisposed to axial fragility fractures despite non-osteoporotic T scores. In addition, osteoporosis screening with DXA is under-utilized in the CLL population, despite meeting age-appropriate screening guidelines. Increased awareness and screening for axial fragility fractures, especially in men and smokers, should be recommended in the long term follow up of patients with CLL. Further study is needed to understand the pathophysiology of osteoporosis and FF in patients with CLL to develop improved methods for prevention of these morbid fractures. Presentation: No date and time listed

ODP595 Case Series Of Idiopathic Hypercalciuria And Secondary Osteoporosis

Abstract Background Secondary causes for low bone density may be present in 30% of women and up to 50% of men with low bone density and osteoporosis. Idiopathic hypercalciuria is associated with lower bone density and higher bone turnover, and an increased risk of fractures. Thiazide diuretics have been used often for treatment for idiopathic hypercalciuriaCase Series: We present a case series of 9 patients who presented for low or declining bone density. They underwent workup for secondary causes of osteoporosis and were noted to have idiopathic hypercalciuria with high bone turnover on initial evaluation. They were started on thiazide diuretics or amiloride and the dose titrated up daily based on their blood pressure tolerance. They were monitored for hypokalemia and hyponatremia. Several of these patients exhibited a > 30% decrease in bone resorption, as measured by urine N-telopeptide on a second fasting specimen. Follow-up bone density at 1 year and 3-year after starting diuretic therapy showed stability or significant increase in bone density. Some of these patients were able to maintain bone density in the osteopenic range on follow up for > 6 years. Conclusion Some patients with idiopathic hypercalciuria may have a more robust response to thiazide diuretics compared to others even in the absence of anti-resorptive therapy. Significant reduction of > 30% in bone resorption markers may identify patients who are more likely to have a robust response in the bone density after starting thiazide medications. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

PSAT182 Dilemmas in the Diagnosis and Management of Osteoporosis in a patient with Alkaptonuria: Successful Treatment with Teriparatide

Abstract Introduction Diagnosis and management of osteoporosis in patients with alkaptonuria can be challenging. Coexisting arthritis involving the lumbar spine (LS) and hips can falsely elevate bone density making DXA interpretation difficult. We report a patient with alkaptonuria who was successfully treated with teriparatide in addition to bisphosphonate therapy. Case History A 69-year-old female presented for evaluation of osteoporosis. She was diagnosed with alkaptonuria at age 29 when she reported bilateral conjunctival hyperpigmentation. She was also diagnosed with arthritis requiring left knee joint replacement at the age of 57 years. Subsequently, she underwent left hip, right knee, right hip, and left shoulder joint replacement surgeries. She also sustained fragility fractures in the foot and a 2-inches height loss. Physical examination: normal vital signs. Examination of eyes and ears: bluish black discoloration of the conjunctiva and ear lobes. Heart examination showed normal S1, split S2, and IV/VI systolic murmur over the right parasternal border; the rest of the physical examination revealed limited joint movements of thoracic and lumbar spines, wrists, ankles, knees and hip joints. Laboratory: serum PTH 33 pg./mL, 25-OH vitamins 28 ng/mL, 1,25 (OH)2 vitamin D 43 pg/mL, osteocalcin 11.6 mg/mL (ref 9.4-47.4), collagen cross-linked C-telopeptide 318 pg/mL (ref 104-1008), tyrosine 79.1 umol/L (ref 31.1-118.1), 24 hours urine homogentisic acid 4.2 gms (ref 20-30 mg). Genetic testing: compound heterozygous mutation for the HGD C. 496T2T>C and HGD C.1102A < G (p.mev368Va) variants, consistent with a diagnosis of alkaptonuria. DXA scan done at the age of 56 years showed osteoporosis (T score -2.7 femoral neck, 1.8 total hip, 2.5 LS). Patient was started on alendronate 70mg PO weekly for 5 years in addition to nitisinone. While on alendronate, she sustained fragility fractures of the right radius and left ankle. After 5 years of alendronate, the patient was transitioned to teriparatide 20-mcg subcutaneously (SC) daily for 2 years followed by annual intravenous zoledronic acid. For the subsequent 7 years, the patient led a healthy, active life with no fractures. Follow-up DXA showed improvement to the osteopenic range at the radius site as degenerative arthritis made interpretation of other sites impossible.This case illustrates the challenges in the diagnosis and treatment of osteoporosis in patients with alkaptonuria. DXA can be ineffective in this condition due to the hip and LS arthritis. Measurement of trabecular bone scoreS and CT of the LS may be better alternate choices. Bisphosphonates alone are typically not effective in preventing fragility fractures in this population but use of teriparatide may be an effective treatment. Further studies are needed to assess the effectiveness of teriparatide in this population but our case shows promise that this treatment result in BMD improvement and fracture prevention. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Clinical predictors of incipient vertebral fractures and bone mineral density in kidney transplant patients.

Kidney transplant recipients are prone to metabolic bone diseases and consequent fractures. This study aimed to evaluate the incidence of incipient vertebral fractures, osteopenia, osteoporosis, and the clinical factors associated with incipient vertebral fractures in a group of kidney transplant patients. Two hundred sixty-four patients (F/M 124/140, 45.3 ± 13years) who had undergone kidney transplantation in tertiary care centers were included. Vertebral fractures were assessed semiquantitatively using conventional thoracolumbar lateral radiography in 202 of the patients. Vertebral fractures were observed in 56.4% (n = 114) of the study group. The frequency of osteoporosis was 20.0% (53 of 264 patients), and osteopenia was 35.6% (94 of 264 patients). Bone mineral density (BMD) levels were in the normal range in 40.3% (n = 46) of the subjects with vertebral fractures. It was in the osteoporotic range in 20.1% (n = 23) and the osteopenic range in 40.3% (n = 46). Vertebral fractures were associated with age, duration of hemodialysis, BMI, and femoral neck Z score (R2 37.8%, p = 0.027). As incipient vertebral fractures can be observed in patients with normal BMD levels in kidney transplant recipients, conventional X-ray screening for vertebral fractures may be beneficial for a proper therapy decision of metabolic bone disease in kidney transplant recipients.

PREVALENCE OF OSTEOPOROSIS IN SUB-URBAN POPULATION OF CHENNAI USING QUS (QUANTITATIVE ULTRASOUND) OF CALCANEUM -A CROSS SECTIONAL STUDY

Background:Burden of Osteoporosis and its related fractures are enormous and growing public health concern. Worldwide, an estimated 200 million adults suffer from osteoporosis. Vertebral and non-vertebral fractures are the most clinically relevant osteoporotic fracture because they are expensive to treat and have severe consequences for middle aged and elderly population.(1 ,2) The purpose of our study was to assess calcaneal ultrasound score as a screening test for osteoporosis. Material and Methods: Fifty patients above the age of 40 years who attended a health checkup camp conducted by our institute in a suburban population base of Chennai,Tamilnadu was subjected for noninvasive QUS of calcaneum bone as a screening test for osteoporosis. They were divided into different age groups ,co-morbid conditions noted and BMD scores from QUS was assessed. Statistical method were used with SPSS Version .It was a cross sectional descriptive study. Results: A total of 50 patients underwent QUS of calcaneum bone in our study , all of them above the age of 40 years. 33(66%) of them were females and 17(34%) were males. Eight patients( 16% ) had T score < -2.5 out of which 1 was male. 26 patients(52%) had T scores in the osteopenic range (-1>Tscore>-2.5).16 patients(32%) had T scores in the normal range. 40 % of patients had associated osteoarthritis and four patients had diabetes. 2 patients who underwent screening had past history of nontraumatic fractures. Conclusion: QUS of calcaneum is a good screening tool for assessing bone density in our country since its cost effective and can be used in various screening camps. The machine is portable and can be used with minimal training making it easier for the primary caregiver. It has reasonably good sensitivity and fair specicity when using Tscore of -2.5 as the cut off point. However DEXAis the gold standard for treatment and followup of patients with osteoporosis.

Clinical Characteristics and Fracture Patterns Among Postmenopausal Women with Isolated Osteoporosis at the Forearm

Patients found to have isolated osteoporosis at the 1/3 radius (1/3RO) represent a therapeutic dilemma. It is unknown whether 1/3RO is associated with an increased risk of fragility fractures, and is therefore unclear whether these patients should be treated similarly to those with osteoporosis at central sites. This retrospective study investigated the clinical significance of 1/3RO by comparing medical history, fracture prevalence, areal BMD, and Trabecular Bone Score in postmenopausal women with 1/3RO (n = 107) to age-matched women with osteoporosis at the hip and/or spine (PMO, n = 214), and to controls without osteoporosis at any site (n = 214). We then compared the clinical and densitometric characteristics among women with 1/3RO according to fracture history. The mean age of the 535 women included in the study was 71 ± 8 yr. Women with 1/3RO had BMD in the osteopenic range at all other sites (mean spine T-score = -1.0, total hip = -1.4, femoral neck = -1.7). Women with 1/3RO reported similar calcium and vitamin D intake, prevalence of primary hyperparathyroidism, chronic kidney disease, and other comorbidities compared to the other groups. The prevalence of an osteoporotic fracture of the spine, hip, wrist, or humerus tended to be higher among women with PMO compared to 1/3RO or controls (PMO: 31%, 1/3RO: 21%, Controls: 23%, p = 0.07). Among women with 1/3RO, fracture prevalence was related to older age. No other clinical characteristic distinguished women with and without fracture. Neither BMD at other sites nor TBS differed according to fracture history. Among postmenopausal women with 1/3RO, those who are older are at an increased risk of fracture, even when T-scores at other sites are well above the osteoporosis threshold. Additional research is needed to confirm our results, and to assess whether treatment should be considered to reduce fracture risk in older women with 1/3RO.

Fracture Risk Assessment: An Update.

Our ability to accurately identify high fracture risk in individuals has improved as the volume of clinical data has expanded and fracture risk assessment tools have been developed. Given its accessibility, affordability, and low radiation exposure, dual x-ray absorptiometry (DXA) remains the standard for osteoporosis screening and monitoring response to treatment. The trabecular bone score (TBS) is a DXA software add-on that uses lumbar spine DXA imaging to produce an output that correlates with bone microarchitecture. It has been identified as an independent fracture risk factor and may prove useful in further stratifying fracture risk among those with a bone mineral density (BMD) in the osteopenic range (-1.0 to -2.4 standard deviations), in those with low-energy fractures but normal or only mildly low BMD, or in those with conditions known to impair bone microarchitecture. Fracture risk assessment tools, including the Fracture Risk Assessment Tool (FRAX), Garvan fracture risk calculator, and QFracture, evaluate the impact of multiple clinical factors on fracture risk, even in the absence of BMD data. Each produces an absolute fracture risk output over a defined interval of time. When used appropriately, these enhance our ability to identify high-risk patients and allow us to differentiate fracture risk among patients who present with similar BMDs. For challenging clinical cases, a combined approach is likely to improve accuracy in the identification of high-risk patients who would benefit from the available osteoporosis therapies.

High prevalence of vertebral fractures in seizure patients with normal bone density receiving chronic anti-epileptic drugs.

Chronic use of antiepileptic drugs (AEDs), both enzyme-inducing (phenytoin, phenobarbital, carbamazepine, and primidone) and non-enzyme-inducing (i.e., valproate), is recognized as acauseof secondary osteoporosis. Vertebral compression fractures (VF) are the most common type of osteoporotic fractures and may confer an increased risk of future hip, wrist, and vertebral fractures. Vertebral compression fractures in the general population are frequently asymptomatic, and under-diagnosed. The purpose of this study is to describe the prevalence of VF in a cohort of male veterans with epilepsy on chronic AEDs. The cohort for this study consisted of 146 male veterans who carried a diagnosis of epilepsy and were chronic users of AEDs known to cause osteoporosis (phenobarbital, phenytoin, carbamazepine, primidone, and valproate). Chronic AED use wasdefined as receiving an AED for at least 2 years. Subjects were previously seen in the osteoporosis clinic and had been evaluated by a dual-energy X-Ray absormetry (DXA) instrument including morphometric studies following a standard vertebral fracture assessment (VFA) protocol during the same DXA imaging acquisition session. The mean age was 63 years. Low bone mineral density defined as osteoporosis or osteopenia was observed in 29% and 43% respectively. We observed at least one VF in 41 % of the subjects who had normal BMD, 54% in the osteopenic range, and 75% in the osteoporotic range. By performing a VFA in addition to standard bone densitometric studies, we disclosed a large prevalence of compression fractures in individuals with epilepsy chronically treated with AEDs who had BMDs in the normal and osteopenic ranges. The addition of VFA or other imaging methods to evaluate VF should be included in the evaluation of bone health in individuals with epilepsy receiving AEDs since it may modify treatment recommendations to prevent future osteoporotic fractures.

Evaluation of Environmental and Socioeconomic Factors Contri-buting to Fragility Fractures in Indians

Objective: Osteoporosis causes fragility fractures that also occur in patients with bone mineral density (BMD) in the normal or osteopenic range, suggesting role of risk factors that are unrelated or partially related to BMD. The study aims at highlighting the link between 3 conditions, that are environment and occupation related risk factors and that are widely prevalent in India, and development of fragility fractures. Methods: A Case Control study was done by rec-ruiting 110 Cases with history of recent fragility fractures and 84 Controls with no history of recent fractures. 3 study parameters, village dwelling, con-ventional farming, and poverty, were chosen the presence or absence of which were documented in participants. This was followed by an ODDS ratio analysis. Results: The Odds of village dwellers, conventional farmers, and socioeconomically poor individuals to develop fragility fractures were both significant and large. Conclusion: Urbanization is a risk in the dev-elopment of fragility fractures. However, this study points that village dwelling in India is associated with the development of fragility fractures. Similarly, Odds of farmers exposed to pesticides and agrochemicals to develop fragility fractures is large and significant. Pesticides and agrochemicals act as endocrine disruptors and bone health is closely linked to endocrine system. Fragility fractures among farmers may be due to endocrine disrupting properties of pesticides and agrochemicals. Socioeconomic deprivation is a known risk in the development of osteoporosis. This study too highlights that the odds of individuals living in poverty to develop fragility fractures is significant and large.

Comparison of Radiographic Singh Index with Dual-Energy X-Ray Absorptiometry Scan in Diagnosing Osteoporosis

Objective: The objective of this study was to assess the accuracy of radiographic Singh index (SI) with respect to dual-energy X-ray absorptiometry (DEXA) scan in diagnosing osteoporosis. Materials and Methods: We conducted a cross-sectional study on 100 postmenopausal women in the Department of Radiodiagnosis, SKIMS, Soura, Srinagar, from June 2019 to December 2019. We obtained right or left standard anteroposterior hip radiograph in each patient and compared its SI grade to the densitometry results obtained from the DEXA study of the corresponding hip. Results: Out of the selected patients, 7% had DEXA bone mineral density (BMD) values in normal range (T-score ≤1), 81% in osteopenic range (T-score >1.00–<2.5), and 12% in osteoporotic range (T-score ≥2.5). There was no statistically significant correlation (r = −0.108, P = 0.286) between SI grade and WHO BMD category (normal, osteopenia, or osteoporosis). There was no statistically significant correlation (r = 0.191, P = 0.057) between the SI grade and the mean absolute DEXA BMD value. There was also no statistically significant correlation (r = −0.195, P = 0.052) between SI grade and mean DEXA T-score. Conclusion: Our study found a poor correlation between radiographic SI and DEXA densitometry results. We concluded that the SI cannot be used as a substitute for DEXA study in diagnosing osteoporosis.

Clinical and biochemical characteristics of adults with hypophosphatasia attending a metabolic bone clinic.

This study sought to identify the clinical and biochemical characteristics that would help distinguish hypophosphatasia (HPP) from other metabolic bone diseases in adult patients attending a metabolic bone clinic by comparing patients who have genetically confirmed HPP with a group of patients with low bone mineral density (BMD) in the osteoporotic or osteopenic range. Data were collected from February 2016 to October 2018 for 41 patients (n=20 in the HPP group, n=21 in the low-BMD group) attending the metabolic bone clinic at Sheffield, United Kingdom (UK) or who were recruited via the Rare UK Diseases Study (RUDY) platform during the same period. A study questionnaire was administered to all patients, and assessments were conducted for laboratory values, physical functions, BMD, and spine imaging. Patients with HPP were characterized as being younger, more likely to have metatarsal or femoral shaft fractures, and less likely to have vertebral fractures compared with patients in the low-BMD group. The HPP group had lower total and bone-specific alkaline phosphatase, higher pyridoxal 5'-phosphate (PLP), and lower, albeit sufficient, 25-hydroxyvitamin D. Low-BMD group had lower C-terminal telopeptide and tartrate-resistant acid phosphatase 5b (61.9% were on bisphosphonates at enrollment). Dual X-ray absorptiometry (DXA) analysis found that the HPP group had higher total hip and lumbar BMD T- and Z-scores compared with the low-BMD group. There were no differences found between the two groups with physical functional assessments. Results of receiver operating characteristic analysis indicated strong diagnostic accuracy of these biomarkers for HPP. Thresholds of total alkaline phosphatase (ALP) activity of 43IU/L or less and PLP level of 120nmol/L or more were determined to be potentially clinically useful for distinguishing HPP from other metabolic bone diseases. This study supported the use of ALP and PLP measurements as predictive of HPP diagnosis along with certain demographic and clinical characteristics (younger age, metatarsal or femoral fractures without low mean BMD T- and Z-scores on a DXA scan) that can aid in recognizing adults who should be further evaluated for HPP. The critical values identified need to be applied to an independent sample to be tested for diagnostic accuracy.

Folate and Vitamin B-12 Status Is Associated With Bone Mineral Density and Hip Strength of Postmenopausal Chinese-Singaporean Women.

ABSTRACTThe role of micronutrients such as folate and vitamin B‐12 in bone quality has been widely studied with conflicting results. Ethnicity seems to play a large role on nutrient intake, as diet varies across cultures. In this study, we examined the relationships of BMD, proximal femur strength, and bone resorption with plasma folate and vitamin B‐12 in a cohort of 93 healthy postmenopausal women of Chinese‐Singaporean descent. The parameters examined were areal (aBMD) and volumetric BMD (vBMD) of the proximal femur and the third lumbar vertebra (L3), total body aBMD, proximal femur bending, compressive and impact strength indices (composite strength indices) and circulating levels of C‐telopeptide of type I collagen. Eighteen participants (19.4%) had aBMD in the osteoporotic range (osteoporosis group), 59 (63.4%) in the osteopenic range (osteopenia group), and the remaining 16 (17.2%) in the normal range (normal BMD group). Circulating folate levels were significantly higher in the normal BMD group compared with the osteoporosis group. Using linear regression analysis, we found that overall, aBMD and vBMD are positively associated with folate concentrations, whereas composite strength indices were positively associated with vitamin B‐12 concentrations. These findings support the existing literature and suggest a link between levels of circulating folate/vitamin B‐12 and BMD/bone strength in the cohort examined. Further investigation is needed to examine if individuals with inadequate circulating levels of these nutrients could decrease their risk for fragility fractures through better nutrition or vitamin supplementation. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Risk factors for vertebral fracture in primary hyperparathyroidism.

Screening for vertebral fractures (VF) in primary hyperparathyroidism (PHPT) is recommended, but there are limited data regarding which patients are at greatest risk for VF. We evaluated risk factors for VF in PHPT. This is a retrospective cross-sectional analysis of 117 participants with PHPT. We assessed Grades 2 and 3 VF by vertebral fracture assessment (VFA) and the association of VF with the trabecular bone score (TBS), other skeletal parameters and clinical risk factors. VFA was performed only in those who met National Osteoporosis Foundation criteria for VFA screening. T-scores were in the osteopenic range and TBS was degraded. Overall VF rate based on VFA or other imaging was 12.8%. Serum PTH, calcium and TBS were not associated with VF. Those with VF were older (p = 0.04), had worse renal function (p = 0.04), were more likely to have received osteoporosis treatment (p = 0.03), and tended to have had a prior fracture (p = 0.06). T-scores did not differ by fracture status at any skeletal site. Those with VF had nine times the odds of osteoporosis at the hip (95% CI 2.4-34.5), but this risk factor had low sensitivity (46.7%) for VF. Hip T-score < -2.6, Age > 78.6 years, and GFR < 58.8 ml/min/1.73 m2 (thresholds maximizing sensitivity and specificity) had areas under the curve of 0.60-0.67 for VF (all p < 0.05) and low sensitivity. Findings were similar when analyses were limited to women. In PHPT, VF risk factors included older age, prior fracture, worse renal function and osteoporosis at the hip, but not osteoporosis at other sites, TBS or biochemical indices of PHPT. Since identified risk factors had low sensitivity and were generally inaccurate for categorizing those with VF, the data do not support limiting screening to PHPT patients with these specific VF risk factors.

Role of Bisphosphonate Therapy in Patients with Osteopenia: A Systemic Review.

By contrast to clinical trials exploring osteoporosis, clinical trials specifically designed for the osteopenic population are limited. Thus, less clinical data are available regarding treatment benefits and cost-effectiveness of treating a patient population with a bone mass density in the osteopenic range (T-score between -1 and -2.5). In this article, we aimed to highlight this high-risk population with a low bone mass density (BMD) susceptible to high fracture risk by reviewing different national and international guidelines for treating osteopenia. The cost-effectiveness of the therapy for the above-mentioned patient population is also discussed. By reviewing different clinical trials, we have specifically highlighted the role of bisphosphonate therapy for fracture risk reduction and increment in bone mineral density (BMD) in patients with osteopenia.

Long-Term Effects of Oral Eliglustat on Skeletal Manifestations of Gaucher Disease Type 1: Results from Four Completed Clinical Trials

Background:In Gaucher disease type 1 (GD1), deficient lysosomal acid β-glucosidase activity leads to accumulation of glucosylceramide and formation of lipid-laden macrophages known as Gaucher cells. Patients experience a range of disease manifestations including anemia, thrombocytopenia, hepatosplenomegaly, and debilitating bone complications that impair quality of life. Hematologists are central to disease recognition and management. Most patients, even those without overt symptoms of bone involvement, have radiologic evidence of bone disease. Eliglustat, an oral substrate-reduction therapy, is a first-line treatment for adults with GD1 who have extensive, intermediate or poor CYP2D6 metabolizer phenotypes (>90% of patients). Oral eliglustat partially inhibits glucosylceramide synthase, thereby reducing glucosylceramide accumulation, unlike enzyme replacement therapy (ERT), the historic standard of care for GD1, which augments acid β-glucosidase activity in mononuclear phagocytes and is administered in biweekly infusions.Methods:We analyzed bone mineral density T- and Z-scores and occurrence of bone pain and bone crises in 4 completed clinical trials sponsored by Sanofi Genzyme that involved 393 GD1 patients treated with eliglustat for 4-8 years: Phase 2 (NCT00358150), Phase 3 ENGAGE (NCT00891202), Phase 3 ENCORE (NCT00943111), and Phase 3 EDGE (NCT01074944). Healthy reference scores are >-1 for T-scores and >-2 for Z-scores. Bone marrow burden (BMB) scores and changes in macrophage inflammatory protein 1β (MIP-1β) were also analyzed in the 3 Phase 3 trials. BMB, an MRI-based scoring system to evaluate marrow infiltration of both the lumbar spine and femur, and MIP-1β, a biomarker produced by inflammatory phagocytes surrounding Gaucher cells, are associated with active and evolving bone disease in GD1.Results:In treatment-naïve patients (Phase 2, N=26; ENGAGE, N=40), mean spine T-scores moved from the osteopenic range (>-2.5 to ≤ -1) at baseline to the healthy reference range after 2-3 years of eliglustat, with continued improvement thereafter in both trials. Mean±SEM spine T-score increased from -1.55±0.28 to -0.59±0.34 (n=14; mean±SEM increase from baseline: 0.96±0.32), after 8 years in Phase 2, and increased to -0.53±0.27 in ENGAGE patients with bone data at 4.5 years (n=9; mean±SEM increase from baseline: 0.53±0.16). Spine Z-scores for both trials showed similar improvements; femur T- and Z-scores in both trails remained in the normal range. In the ENCORE trial of patients stabilized after a mean of 10 years of ERT (N=157), T- and Z-scores (spine and femur) remained in the reference ranges for up to 4 years; least square mean spine Z-scores improved by 0.29 (P<0.0001). In EDGE (N=170, mostly ERT switch), randomized patients stabilized on eliglustat during a 6- to 18-month Lead-In Period maintained normal T- and Z-scores (spine and femur) through the dose regimen arm of the study and the succeeding extension period. Mean total BMB scores improved from 10 (in the marked to severe range) to 8 (moderate range) in ENGAGE (treatment-naive patients), and remained stable at 8 throughout ENCORE and EDGE (switch/mostly switch patients). The proportion of patients experiencing recent (≤4 weeks) bone pain decreased after treatment in all 4 trials, and reported pain became less severe. No patient in Phase 2 or ENGAGE had a bone crisis while on eliglustat. Bone crises were reported in 3/157 (1.9%) ENCORE patients over the trial duration. In EDGE, the only trial to enroll patients with active bone disease, 6/170 (3.5%) patients had bone crises during the trial, 3 of whom had bone crises during the 6 months prior to trial entry. Bone crises decreased with increasing time on eliglustat, with only 1 bone crisis reported during the 2- to 3-year trial extension. In ENGAGE (treatment-naïve), median MIP-1β levels elevated 3-fold at baseline normalized. In ENCORE and EDGE (switch/mostly switch), MIP-1β levels remained in the normal range. Across the 4 trials, most adverse events were mild/moderate (97%) and considered unrelated to eliglustat (86%); 9 (2.3% overall) patients withdrew due to adverse events considered drug-related.Conclusions:Long-term eliglustat treatment induced continued improvement in bone parameters in treatment-naïve patients. These parameters remained stable in trials involving patients who had been previously treated. Eliglustat was generally well-tolerated. DisclosuresMistry:Sanofi Genzyme: Honoraria, Other: Principal Investigator for the eliglustat ENGAGE and ENCORE trials; ReceivedTravel Reimbursement; Member of the ICCG North American Advisory Board; , Research Funding. Charrow:Sanofi Genzyme: Honoraria, Other: Principal investigator, eliglustat EDGE trial; Member of advisory boards, Research Funding. Cox:Sanofi Genzyme: Honoraria, Other: Principal investigator for the eliglustat ENCORE trial; received travel reimbursement, Research Funding. Lukina:Sanofi Genzyme: Honoraria, Other: Principal investigator in the eliglustat Phase 2, ENGAGE, ENCORE, and EDGE trials; receives travel reimbursement; member of advisory boards, Research Funding. Marinakis:Sanofi Genzyme: Other: Principal investigator for the eliglustat EDGE trial, Research Funding. Foster:Sanofi Genzyme: Employment. Gaemers:Sanofi Genzyme: Employment. Peterschmitt:Sanofi Genzyme: Employment.

Abnormal microarchitecture and stiffness in postmenopausal women using chronic inhaled glucocorticoids.

While oral glucocorticoids are well recognized to have destructive skeletal effects, less is known about the effects of IGCs. The detrimental skeletal effects of IGCs may be greatest in PM women, in whom they compound negative effects of estrogen loss and aging. The goal of this study was to evaluate microarchitecture and stiffness in PM women using chronic IGCs. This case-control study compared PM women using IGCs for ≥ 6months (n = 20) and controls matched for age and race/ethnicity (n = 60). Skeletal parameters assessed included areal BMD (aBMD) by DXA, trabecular and cortical vBMD and microarchitecture by HRpQCT of the radius and tibia, and whole bone stiffness by finite element analysis. By DXA, mean values in both groups were in the osteopenic range; hip aBMD was lower in IGC users (P < 0.04). By HRpQCT, IGC users had lower total, cortical, and trabecular vBMD at both radius and tibia (all P < 0.05). IGC users had lower cortical thickness, lower trabecular number, greater trabecular separation and heterogeneity at the radius (all P < 0.03), and greater heterogeneity at the tibia (P < 0.04). Whole bone stiffness was lower in IGC users at radius (P < 0.03) and tended to be lower at the tibia (P = 0.09). PM women using IGCs had substantial abnormalities in vBMD, microarchitecture, and stiffness compared to controls. These abnormalities were most severe at the radius. These preliminary results suggest that there may be major, heretofore unrecognized, skeletal deficits in PM women using IGCs.

Study of bone mineral density and their determinants among Medical practitioners of a Tertiary care Government hospital

Background Vitamin D deficiency prevails in epidemic proportions all over the Indian subcontinent with a prevalence of 70ndash100 in the general population. Hence it is important to estimate its burden in doctors and other health care providers.Objectives 1. To test Bone Mineral Density BMD values using Dual Energy X-Ray Absorptiometry DEXA scan among the study population. 2. To correlate values of Bone Mineral Density with serum 25-OH cholecalciferol serum calcium weight height body mass index BMI sun exposure physical activity and diet. 3. To document known co-morbidities among study population.Methodology The study is a prospective cross sectional study.50 medical practitioners adhering to the inclusion and exclusion criteria of the study were invited for participation with voluntary consent. Their Bone Mineral Density values were calibrated by using an Ultrasound based Bone mineral densitometer having a 1 MHz transducer probe. Serum Vitamin D values were estimated by radioimmunoassay method and were expressed in nmolL. Serum Calcium values were estimated by semiauto-analyzer.Results 58 of study population had normal bone mineral density. Only 12 had normal serum vitamin D. There was no significant association between bone mineral density and serum VitaminD. Conclusion The Bone Mineral Density BMD values in the study population are on an average in the osteopenic range with low serum vitamin D levels.