Management Of Bone Health Research Articles

Abstract P4-10-19: Aromatase inhibitors and bone health in elderly women with early breast cancer: Real-world data

Abstract Introduction: Aromatase inhibitors (AI) are the mainstay therapy for postmenopausal women with hormone receptor-positive early breast cancer (HR+ EBC). However, their use induces alterations in bone homeostasis, increasing the risk of osteoporosis and fractures, thus impairing quality of life. Elderly women commonly have decreased bone density at the time of EBC diagnosis and AI initiation. Also, this population is usually underrepresented in clinical trials, thus causing scarcity in available data to study the AI long-term effects on bone density among seniors. Hence, we aimed to assess in a real-world setting the clinical impact of bone health management (BHM) in elderly women undertaking AI. Methods: We conducted a 3-year retrospective cohort study of women with HR+ EBC under adjuvant therapy with AI. Patients were stratified according to age: 65-74 (A group) and ≥75 (B group) years old. Statistical analysis of collected data was performed using IBM SPSS v25.0. and StataIC v5.0. Results: A total of 282 patients was included. The median age was 74 years (65-98) and 48.6% of patients enrolled (n=137) were ≥75 years. The median time under AI was 50 months (1-108). AI-associated arthralgia was higher in the elderly group (46.7% vs. 34.5%; p=0.036) that also reported a significantly higher rate of treatment suspension due to AI intolerance (5% vs. 1%; p=0.025). Baseline bone densitometry (BBD) was carried out in a sample of 65.6% of patients and revealed osteopenia or osteoporosis in 82.2% of the sampled individuals. Despite that, only 68.8% and 16.6% of them started calcium/vitamin D supplementation and bisphosphonates therapy, respectively. The incidence of fracture was higher in the B group (17.5% vs. 8.3%; p=0.020), mostly in the radium (25%) and secondary to a fall. Increasing age (p=0.01) and history of previous fracture (p=0.07) independently predicted a fracture event in group B. Adjusting for intrinsic subtype and disease staging, patients with a fracture event had lower disease free-survival (DFS) (HR 4.25 95% CI 0.9-22, p=0.08), but these results were noted only in group A. Conclusions: Our study challenges some perceptions regarding the attention given to bone health in everyday practice. The clinicians' adherence to published guidelines on BHM was overall low, with BBD being performed in only two-thirds of patients. On the positive side, a few clinical suggestions spring from our results. The higher AI intolerance among elderly women opens the opportunity for alternative therapies, such as Selective Estrogen Receptor Degraders (SERD). Fall-preventive strategies should also be implemented especially in high-risk groups such as elderly women under AI. These practice recommendations are likely to foster quality of care and reduce private and public health costs. Citation Format: Mafalda Miranda Baleiras, Leonor Vasconcelos de Matos, Leonor Fernandes, Maria Teresa Neves, Fátima Alves, André Ferreira, Helena Miranda, Ana Martins. Aromatase inhibitors and bone health in elderly women with early breast cancer: Real-world data [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-10-19.

Marijuana in Orthopaedics: Effects on Bone Health, Wound-Healing, Surgical Complications, and Pain Management.

Marijuana use is on the rise in the United States, and there is a paucity of information on the effects of cannabis and its chemical constituents on bone health, wound-healing, surgical complications, and pain management. Current evidence suggests that cannabidiol (CBD) may enhance bone health and metabolism, while Δ9-tetrahydrocannabinol (Δ9-THC), the major psychoactive component in marijuana, has an inhibitory effect. Marijuana users are at higher risk for delayed bone-healing, demonstrate lower bone mineral density, are at increased risk for fracture, and may experience postoperative complications such as increased opioid use and hyperemesis.

Patients experience a need for informal care after a fragility fracture.

In individuals with fragility fractures, our objectives were to examine (1) the experience of receiving informal care post-fracture; and (2) how these care experiences influenced post-fracture recovery and subsequent management of bone health. A secondary analysis of six primary qualitative studies was conducted. Individuals in the primary studies were English-speaking women and men, 45years and older, who were living in the community and had sustained a recent fragility fracture or reported a history of previous fragility fractures. Participants who reported at least one instance of needing informal care were categorized as receiving "enough care", "insufficient care", or "no care". Of 145 participants in the primary studies, 109 (75%) described needing informal care after their fracture. Of those needing care, 62 (57%) were categorized as receiving enough care while 47 (43%) were categorized as receiving insufficient or no care. The care needed affected the management of participants' fracture and bone health, including access to health care services. Participants who received insufficient or no care, especially those living alone, devised strategies to care for themselves and often requested help from multiple individuals to minimize the burden to family and friends. Compared with men, women appeared to report needing help with personal daily activities, such as bathing, and transportation to appointments related to bone health. Informal care needs are an additional burden of fragility fractures. Post-fracture interventions should consider the broader context of patients' lives and potentially support the care needs of patients as part of their services.

Attention to bone health in follow-up of gynaecological cancers in tertiary care.

Objective:Women with gynaecological cancers are at an increased risk of cancer treatment–induced bone loss, which impacts on their quality of life and overall survival. Clinical cancer follow-up reviews focus on cancer status and fail to attend to important health and quality-of-life issues. We questioned whether there was a care-gap between tertiary clinicians and primary care physicians in the management of bone health in this cohort. Significant care-gaps in relation to bone health have been demonstrated in other oncologic settings. The objective of this study was to determine the level of attention to bone health in the care of women living with and beyond gynaecological cancer at a tertiary referral centre for gynaecological oncology.Methods:Retrospective, observational cohort study of attention to bone health in the management and follow-up of gynaecological cancers.Results:This study shows that there has been suboptimal attention from the carers at a cancer centre to bone health during the oncological follow up of women undergoing treatment for gynaecological cancer. In those at particular risk of cancer treatment–induced bone loss (iatrogenic menopause and/or external beam pelvic radiotherapy), 52% of women had no reference to bone health in their notes, and 57% had no assessment of bone mineral density.Conclusion:Tertiary cancer carers may underestimate the importance of bone health or believe that it falls outside the remit of their gynaecologic oncology service. Further research is needed to explore whether these findings are indicative of a true care gap and to gain insight into possible corrective measures.

Relationships Between Pulmonary Function and Composite Indices of Femoral Neck Strength in Korean Men (KNHANES IV).

BackgroundDespite the close relationship between osteoporosis and chronic pulmonary diseases, few studies have evaluated relationships between pulmonary functions and bone quality. We investigated associations between pulmonary function test results and femoral neck strength indices (SIs) in Korean men.MethodsThis population-based, cross-sectional study was conducted using data from the Korea National Health and Nutrition Examination Survey IV on 936 men aged ≥ 19 years. Pulmonary functions (forced vital capacity [FVC] and forced expiratory volume in one second [FEV1]) were measured using a dry rolling seal spirometer. Femoral neck SIs, relative to load, were calculated by hip dual-energy X-ray absorptiometry for compression strength index (CSI), bending strength index (BSI), and impact strength index (ISI).ResultsThe 443 (47.3%) of the 936 men were current smokers. FVC, FVC percentage with respect to the expected normal value, FEV1, and FEV1 percentage with respect to the expected normal value (FEV1p) were positively associated with CSI and BSI after adjusting for confounders, including smoking history (β = 0.003–0.223, P = 0.005–0.036). FEV1 and FEV1p were positively associated with ISI (β = 0.000–0.014, P = 0.010–0.025). Of components of femoral neck SIs, bone mineral density was correlated with FEV1 and FEV1p (β = 0.001–0.037, P = 0.017–0.019). After adjusting for all confounders, all femoral neck SIs increased with FVC quintiles (P for trends = 0.001–0.012), and CSI and BSI increased with FEV1 quintiles (P for trends = 0.034–0.043).ConclusionReduced pulmonary function was correlated with reduced femoral neck strength, even after adjusting for smoking history in Korean men. Femoral neck SIs might be useful tools for evaluating bone health in men with reduced pulmonary function.

Initiation of bone-targeted agents in patients with bone metastases and breast or castrate-resistant prostate cancer actively treated in routine clinical practice in Europe.

Guidelines recommend starting bone-targeted agents (BTA), such as zoledronic acid and denosumab, as soon as bone metastases (BMs) are definitively diagnosed in all patients with breast cancer (BC) or castration-resistant prostate cancer (CRPC) whether they are symptomatic or not. Data were analyzed from 1364 patients with BC and 1161 patients with CRPC who had BMs and were receiving anti-cancer therapy in hospitals across six European countries (Belgium, France, Germany, Italy, Spain and the UK). The 731 physicians (medical oncologists or urologists) provided insights in the decision-making factors driving their management of bone health for these patients, and the patient medical records indicated how these decisions were reflected in routine clinical practice. Within three months of a BM diagnosis, 74% of BC and 51% of CRPC patients had initiated treatment with a BTA. Around 12% of BC and 23% of CRPC patients did not receive a BTA following BM diagnosis. Irrespective of the tumour type (BC or CRPC), most physicians prescribed either denosumab or zoledronic acid as first BTA therapy. Physicians reported bone pain as a major decision-making factor to initiate a BTA. The presence of bone complications at BM diagnosis and bone pain at BM diagnosis were found to be significant predictive factors for a BTA initiation, irrespective of tumour type. Despite European Society for Medical Oncology (ESMO) guidance on bone protection irrespective of symptomatic disease, not all patients with BMs received a BTA following a BM diagnosis. This suggests that clinical judgements and patients' communication of their pain to their physicians contributed to the decision to prescribe bone protection therapy in cancer patients.

Feasibility and Safety of Physical Exercise to Preserve Bone Health in Men With Prostate Cancer Receiving Androgen Deprivation Therapy: A Systematic Review.

ObjectiveMen with prostate cancer (PCa) receiving androgen deprivation therapy (ADT) experience the loss of bone mineral density (BMD) and lean body mass, which can increase their risk of falls and fractures. Physical exercise programs with appropriate components and dosage are suggested to preserve BMD and muscle strength, thereby potentially reducing accidental falls and fractures and associated morbidity and mortality. These benefits can be obtained if exercise programs are feasible and safe and if patient adherence is adequate. This systematic review investigates the feasibility and safety of exercise programs aimed at preventing the risk of accidental falls and fractures and BMD loss in men with PCa undergoing ADT.MethodsMEDLINE, Embase, CINAHL, and the Cochrane Library were searched from database inception to June 7, 2021. Randomized controlled trials were included when they analyzed the feasibility and safety of experimental exercise programs targeting bone health in men with PCa receiving ADT. Two reviewers independently selected the studies, assessed their methodological quality, and extracted the data. Exercise feasibility was measured through recruitment, retention, and adherence rates. Exercise safety was measured through the number, type, and severity of adverse events. Furthermore, the components, setting, intensity, frequency, and duration of exercise programs were extracted.ResultsTen studies were included, with a total of 633 participants. Exercise consisted of a combination of aerobic, resistance, and impact-loading exercise or football training. Exercise is feasible in men with PCa undergoing ADT, although football training should be prescribed with caution for safety reasons.ConclusionMulticomponent exercise programs targeting bone health seem feasible and safe in this population; however, adverse events should be systematically documented according to current guidelines.ImpactThe study shows that men with PCa receiving ADT can safely perform exercise programs to preserve bone health and supports that those programs should become part of lifestyle habits.Lay SummaryMen with PCa who are receiving ADT can safely perform exercise programs to preserve bone health and should make exercise an important part of their lifestyle.

Management of women's bone health in the gynecological setting: when and how?

Management of women's bone health in the gynecological setting: when and how?

Best Practice Guidelines for Assessment and Management of Osteoporosis in Adult Patients Undergoing Elective Spinal Reconstruction.

Expert consensus study. This expert panel was created to establish best practice guidelines to identify and treat patients with poor bone health prior to elective spinal reconstruction. Currently, no guidelines exist for the management of osteoporosis and osteopenia in patients undergoing spinal reconstructive surgery. Untreated osteoporosis in spine reconstruction surgery is associated with higher complications and worse outcomes. A multidisciplinary panel with 18 experts was assembled including orthopedic and neurological surgeons, endocrinologists, and rheumatologists. Surveys and discussions regarding the current literature were held according to Delphi method until a final set of guidelines was created with over 70% consensus. Panelists agreed that bone health should be considered in every patient prior to elective spinal reconstruction. All patients above 65 and those under 65 with particular risk factors (chronic glucocorticoid use, high fracture risk or previous fracture, limited mobility, and eight other key factors) should have a formal bone health evaluation prior to undergoing surgery. DXA scans of the hip are preferable due to their wide availability. Opportunistic CT Hounsfield Units of the vertebrae can be useful in identifying poor bone health. In the absence of contraindications, anabolic agents are considered first line therapy due to their bone building properties as compared with antiresorptive medications. Medications should be administered preoperatively for at least 2 months and postoperatively for minimum 8 months. Based on the consensus of a multidisciplinary panel of experts, we propose best practice guidelines for assessment and treatment of poor bone health prior to elective spinal reconstructive surgery. Patients above age 65 and those with particular risk factors under 65 should undergo formal bone health evaluation. We also established guidelines on perioperative optimization, utility of various diagnostic modalities, and the optimal medical management of bone health in this population.Level of Evidence: 5.

Identification and pharmacokinetics of bioavailable anti-resorptive phytochemicals after oral administration of Psoralea corylifolia L.

Osteoporosis and resulting bone fractures are the major health issues associated with morbidity in the aging population; however, there is no effective treatment that does not cause severe side effects. In East Asia, dried seeds of Psoralea corylifolia L. (PC) have traditionally been used as an herbal medicine to manage urinary tract, cutaneous, and gastrointestinal disorders, as well as bone health. However, the mechanism of action and active biocomponents of PC are unclear. Here, we adopted a pharmacokinetic (PK) study aiming to identify the bioavailable phytochemicals in aqueous and ethanolic extracts of PC (APC) and (EPC), respectively. In addition, we aimed to determine anti-resorptive constituents of PC, which accounted for its beneficial effects on bone health. To this end, we used ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). A rapid, sensitive, and reliable UPLC-MS/MS method was developed and determined the 17 PC ingredients. In the PK study, nine components (two chalcones, two coumarins, one coumestan, two flavonoids, and two isoflavonoids) were observed between 36 and 48 h after oral administration of APC or EPC. Among the bioavailable ingredients, four PC constituents (psoralidin, isobavachin, corylifol A, and neobavaisoflavone) inhibited M-CSF-and RANKL-induced osteoclast differentiation in bone marrow-derived macrophages. In addition, two chalcones and two isoflavonoids markedly inhibited cathepsin K activity, and their binding modes to cathepsin K were determined by molecular docking. In summary, our data suggest that bioavailable multicomponents of PC could contribute to the management of bone health.

Characterization of sleep-disordered breathing in children with Duchenne muscular dystrophy by the American Academy of Sleep Medicine criteria vs disease-specific criteria: what are the differences?

Individuals with Duchenne muscular dystrophy (DMD) frequently develop sleep-disordered breathing. Noninvasive ventilation is often prescribed for sleep-disordered breathing treatment based on the American Academy of Sleep Medicine (AASM) criteria. In 2018, DMD disease-specific criteria for sleep-disordered breathing were established. Our study aimed to examine the clinical interpretation differences using these different criteria. We performed a multicenter, retrospective chart review of children with DMD followed at The Hospital for Sick Children, Toronto, Canada, and Rady Children's Hospital, San Diego, California, who underwent polysomnography from August 1, 2012, to February 29, 2020. Baseline characteristics and polysomnography data were summarized using descriptive statistics. Agreement for the diagnosis of sleep-disordered breathing evaluated by kappa statistics and sensitivity/specificity analysis was assessed. One hundred five male children with DMD (mean ± SD age: 12.1 ± 3.8 years; body mass index z score: 0.2 ± 2.3) were included. The proportions of children with DMD that met at least 1 AASM criterion and at least 1 DMD criterion were 45.7% and 67.6%, respectively. We found that 32.4% of children met neither AASM nor DMD criteria. Overall agreement between AASM and DMD criteria was moderate (k = 0.57). There was almost perfect agreement in sleep apnea diagnosis (k = 0.90); however, there was only slight agreement in hypoventilation diagnosis (k = 0.12) between AASM and DMD criteria. There were more children with DMD diagnosed with nocturnal hypoventilation and prescribed noninvasive ventilation using DMD criteria compared with AASM criteria. Future studies should address whether the prescription of noninvasive ventilation for children with DMD based on both criteria is associated with different clinical outcomes. Hurvitz MS, Sunkonkit K, Massicotte C, Li R, Bhattacharjee R, Amin R. Characterization of sleep-disordered breathing in children with Duchenne muscular dystrophy by the American Academy of Sleep Medicine criteria vs disease-specific criteria: what are the differences? J Clin Sleep Med. 2022;18(2):609-615.

Effects of exercise training on bone mineral density in adults living with HIV: a retrospective study

Background: Evidence on the effects of exercise training on the bone health of men and women living with HIV (MLHIV and WLHIV) is limited. Objective: To investigate the effects of a long-term multimodal exercise program on the bone mineral density (BMD) of MLHIV and WLHIV. Methods: A retrospective cohort of 39 patients (13 women; 48.4 ± 7.6 y; HIV-infection for 15.5 ± 6.5 y; combined antiretroviral therapy for 12.2 ± 7.0 y) performed a multimodal exercise program (60-min sessions of aerobic, resistance, and flexibility exercises performed 3 times/week for 9–106 months). MLHIV and WLHIV were allocated into groups showing either advanced osteopenia/osteoporosis or normal BMD (+ or −). Results: MLHIV+ increased BMD at the femoral neck, total femur, and lumbar spine (∼3–4%) compared to MLHIV− (p ≤ 0.03). Changes in whole-body BMD were similar between MLHIV groups (p = 0.55). WLHIV+ exhibited higher loss of BMD at the femoral neck (∼6%) than WLHIV− (p = 0.04), whereas reductions in the whole-body, total femur, and lumbar spine (∼3–5%) were similar between groups (p ≥ 0.25). Among men, changes in femoral neck BMD were inversely correlated to femoral neck T-score (r = −0.62; p < 0.001), but not to the time of follow-up, appendicular skeletal muscle mass (ASM) index, or age (p ≥ 0.08). In women, these changes were inversely correlated with time of follow-up (r = −0.58) and age (r = −0.70) and positively correlated with femoral neck T-score (r = 0.46) and ASM index (r = 0.47) (p < 0.01). Conclusion: Multimodal exercise training may improve the BMD in people living with HIV, especially men with advanced osteopenia/osteoporosis. Adjuvant therapies to exercise should be considered to counteract losses in WLHIV.

196. Best practice guideline on the assessment and management of osteoporosis in adult patients undergoing elective spinal reconstruction

<h3>BACKGROUND CONTEXT</h3> Poor bone health in patients undergoing reconstructive spine surgery can lead to complications such as vertebral fractures, pseudarthrosis, proximal junctional kyphosis, and instrumentation failure. No guidelines currently exist for the management of osteoporosis and osteopenia in patients undergoing spinal reconstructive surgery. This expert panel was created to establish best practice guidelines to identify and treat patients with poor bone health prior to undergoing elective spinal reconstruction. <h3>PURPOSE</h3> An expert panel to define best practice guidelines for the assessment and management of osteoporosis in patients undergoing elective spinal reconstruction. <h3>STUDY DESIGN/SETTING</h3> Expert panel, consensus study. <h3>OUTCOME MEASURES</h3> Consensus above 70% on final statements. <h3>METHODS</h3> A multidisciplinary panel with 20 experts was assembled including orthopedic and neurological surgeons, endocrinologists, and rheumatologists. Three rounds of surveys and discussions regarding the current literature were held until a final set of guidelines was created with over 70% consensus. <h3>RESULTS</h3> A total of 21 statements were included in the final survey. Bone health should be considered in every patient prior to elective spinal reconstruction. All patients above 65 and those under 65 with particular risk factors (chronic steroid use, high fracture risk or previous fracture, limited mobility, and eight other key factors) should have a formal bone health evaluation prior to undergoing surgery. DEXA scans of the hip are preferable due to their wide availability. Opportunistic CT Hounsfield Units can be useful in identifying poor bone health. Patients with osteoporosis and osteopenia should be appropriately optimized prior to elective surgery. In the absence of contraindications, teriparatide and abaloparatide are considered first-line agents due to their bone building properties as compared to antiresorptive medications such as bisphosphonates. These treatments should be administered preoperatively for at least 2 months and postoperatively for at least 8 months. <h3>CONCLUSIONS</h3> Based on the consensus of a multidisciplinary panel of experts, we propose best practice guidelines for assessment and treatment of poor bone health prior to elective spinal reconstructive surgery. Patients above age 65 and those with particular risk factors under 65 should undergo formal bone health evaluation. We also reached consensus on perioperative optimization, utility of various diagnostic modalities, and the optimal medical management of bone health in this population. We believe that these guidelines will help reduce adverse postoperative outcomes related to bone health <h3>FDA DEVICE/DRUG STATUS</h3> Teriparatide, abaloparatide, bisphosphonates: Approved.

Bone Health in Patients With Prostate Cancer: An Evidence-Based Algorithm.

The veteran population has an increasingly high number of patients who have either survived, are currently living with, or are being treated for prostate cancer. Survivorship concerns related to the treatment of this disease is a relevant topic in the Veterans Health Administration, given the longevity of life with localized disease treatment and the fairly durable therapies for metastatic disease. Long-term androgen deprivation therapy (ADT) forms the backbone of treatment for advanced and metastatic castration-sensitive prostate cancer. The potential bone-health complications resulting from treatment with ADT should be recognized as many patients live for prolonged periods with stable or controlled disease. It is well established that prolonged ADT can lead to significant bone loss and increased fracture risk, which increases all-cause mortality and disability. Bone-remodeling agents, such as bisphosphonates and receptor-activated nuclear factor κ-B ligand inhibitors, are recommended to reduce the risk of fragility fractures in patients at high risk due to diminished bone density while on hormone deprivation therapy for hormone-naive prostate cancer. These agents are also indicated at a higher dose to prevent complications from bone metastases in castration-resistant prostate cancer with bone metastases. This article reviews recent studies on bone health in men with prostate cancer and presents an evidence-based algorithm for bone-health monitoring during treatment and recommended interventions.

High Prevalence and Incidence of Fractures in Patients Treated for Aggressive B-Cell Non-Hodgkin Lymphomas

▪IntroductionPatients with non-Hodgkin lymphoma (NHL) are diagnosed at a median age of 67, with about 70% surviving over 5 years. The chemotherapy regimens for aggressive NHL includes cyclophosphamide and high doses of corticosteroids, which can result in significant bone loss. Previous studies have shown that fracture incidence approaches 30% by 10 years post-therapy and can impair quality of life of NHL survivors. However, there are no guidelines for bone health management in NHL patients, and additional screening for osteoporosis can be cumbersome and thus not routinely done. By reviewing standard of care pre- and post-treatment CT scans, we aim to evaluate the prevalence and incidence of fractures in patients treated for aggressive B-cell NHL.MethodsIn this retrospective single-center study, we reviewed patients seen at the University of California San Francisco lymphoma clinic in the last year who met the following criteria: 1) had aggressive B-cell NHL excluding primary central nervous system lymphoma, 2) received first-line therapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or similar regimens such as with the addition of etoposide (R-EPOCH), 3) had baseline and post-treatment chest/abdomen/pelvis CT scans available for review. Baseline clinical characteristics and treatment information were collected from review of medical records. Axial CT images as well as sagittal and coronal reconstructions of chest/abdomen/pelvis CT images obtained at baseline and up to 2 years post-treatment were reviewed and graded by 2 radiologists to identify prevalent and incident fractures of the vertebrae, ribs, and pelvis. Exploratory analyses were performed using STATA, and comparisons between groups with or without fractures were performed with t-test or chi-squared test.ResultsWe identified 82 patients who met the inclusion criteria. Patients were diagnosed from 6/1/2007 to 11/15/2016. Median age of diagnosis was 62, with range 19-87. The most common NHL subtype was diffuse large B-cell lymphoma (93%). Patients were primarily treated with R-CHOP (63%) or R-EPOCH (34%) as first-line therapy for a median of 6 cycles, with 90% achieving complete response, 5% partial response, and 5% progressive disease. At the time of diagnosis, 13% of patients had a known diagnosis of osteopenia, osteoporosis, or prior fracture. Baseline clinical characteristics and treatment information are described in Table 1.Of the 82 patients, 23 (28%) were found to have prevalent fractures at the time of diagnosis, with predominantly vertebral fractures. Of those with prevalent fractures, only 5 had a known diagnosis of osteoporosis or prior fracture. After treatment initiation, 2 patients developed progressive fractures and 8 (10%) patients developed new incident fractures, including 5 patients who had prevalent fractures. Compared to those who did not have prevalent fractures, patients with prevalent fractures were more likely to be older (70.9 vs 53.9, p<0.0001) and have a diagnosis of osteopenia, osteoporosis, or prior fracture at baseline (p=0.037). Patients with prevalent fractures also exhibited a trend towards more advanced stage (p=0.052) and higher international prognostic index score (p=0.060).ConclusionsUsing a novel approach of reviewing routinely performed pre- and post-treatment CT scans with sagittal and coronal reconstructions for the evaluation of bone health, we found that newly diagnosed patients with aggressive B-cell NHL have a 28% prevalence of fractures at diagnosis and 10% incidence of new fractures within 2 years of treatment. These rates greatly exceed the reported 15% prevalence of vertebral fractures and 0.5% annual incidence in the general population aged 65-70 (J Bone Miner Res. 2005 Jan;20(1):131-40). The high prevalence of fractures at diagnosis suggests a disease-related process that compromises bone health, and treatment-related bone loss further increases the risk of fractures. In ongoing studies, we seek to use CT-derived measures of bone mineral density and other clinical characteristics to derive a prediction score to identify patients at high risk of developing incident fractures who may benefit from preventative therapies. [Display omitted] DisclosuresAi:Celgene: Research Funding. Andreadis:Amgen: Research Funding; Genentech Inc.: Employment, Equity Ownership, Honoraria; Cellerant Therapeutics: Research Funding; Astellas: Honoraria; Novartis Pharmaceuticals Corporation: Honoraria, Research Funding; Pharmacyclics: Research Funding; Incyte Pharmaceuticals: Research Funding; Gilead Sciences: Honoraria; Seattle Genetics: Honoraria.

Critical review of bone health, fracture risk and management of bone fragility in diabetes mellitus.

The risk of fracture is increased in both type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). However, in contrast to the former, patients with T2DM usually possess higher bone mineral density. Thus, there is a considerable difference in the pathophysiological basis of poor bone health between the two types of diabetes. Impaired bone strength due to poor bone microarchitecture and low bone turnover along with increased risk of fall are among the major factors behind elevated fracture risk. Moreover, some antidiabetic medications further enhance the fragility of the bone. On the other hand, antiosteoporosis medications can affect the glucose homeostasis in these patients. It is also difficult to predict the fracture risk in these patients because conventional tools such as bone mineral density and Fracture Risk Assessment Tool score assessment can underestimate the risk. Evidence-based recommendations for risk evaluation and management of poor bone health in diabetes are sparse in the literature. With the advancement in imaging technology, newer modalities are available to evaluate the bone quality and risk assessment in patients with diabetes. The purpose of this review is to explore the pathophysiology behind poor bone health in diabetic patients. Approach to the fracture risk evaluation in both T1DM and T2DM as well as the pragmatic use and efficacy of the available treatment options have been discussed in depth.

Cancer Treatment–Induced Bone Loss and Role of Denosumab in Nonmetastatic Prostate Cancer: A Narrative Review

AbstractBone loss is an important complication of prostate cancer and its associated treatments, especially androgen-deprivation therapy (ADT). There is a 5 to 10 times increased loss of bone mineral density (BMD) in men receiving ADT with yearly 4 to 13% BMD loss. The risk of fracture increases yearly by 5 to 8% with ADT. ADT associated bone loss of 10 to 15% of BMD doubles the risk of fractures. Hence, BMD evaluation through dual-energy X-ray absorptiometry and evaluation of individual fracture risk assessed before initiating ADT. The use of vitamin D, calcium, bisphosphonates, and denosumab has shown improved bone health in men with prostate cancer receiving ADT. Denosumab 60 mg is approved to increase bone mass in men at high risk for fractures receiving ADT for nonmetastatic prostate cancer. Denosumab has shown improvement of 5.6% BMD at 2 years in nonmetastatic prostate cancer patients, with significant improvements seen at the total hip, femoral neck, and distal third of the radius. Denosumab has shown a 62% decreased incidence of new vertebral fractures at 36 months. Furthermore, denosumab delays the onset of bone metastases in high-risk nonmetastatic prostate cancer patients. Denosumab can be preferred over other bone modifying agents owing to several advantages, such as subcutaneous administration and no requirement of hospitalization, no dose modifications in renal impairment and less incidence of acute phase anaphylactic reactions. We review the available evidence of denosumab for managing bone loss in nonmetastatic prostate cancer patients. The relevant articles used in this narrative review were obtained through general search on google and PubMed using the key terms “non-metastatic prostate cancer,” “denosumab,” “bone loss,” “bone mineral density,” “fracture,” “CTIBL,” and “chemotherapy induced bone loss.”

Second-generation hormonotherapy in prostate cancer and bone microenvironment.

Prostate cancer (Pca) is the most commonly diagnosed cancer affecting men in France. Before the age of 75 years old, 1 in 8 French men will have Pca. Androgen deprivation therapies (ADT) remain the standard of care. Such therapies induce significant bone loss. The bone-remodelling cycle depends on the androgen synthesis signalling pathways. Furthermore, age-specific hormonal decline plays a key role in the decrease in bone mass. As a result, the older the patients, the more likely they are to have osteoporosis if they are treated with hormone therapy. Their risk of osteoporotic fracture has an impact on their quality of life and their capacity of independent living. In recent years, newer hormone therapies (acetate abiraterone, enzalutamide, apalutamide and darolutamide) have proved efficient in metastatic castration-resistant Pca (mCRPC) patients as well as in hormone naïve patients, and actually in nonmetastatic diagnosis. The combination of these treatments with ADT highly inhibit androgen production pathways. They are prescribed to aged patients undergoing bone density loss after first-generation antiandrogen treatment. Specific recommendations for bone health management in Pca patients are currently lacking. To date, bone mineral density in patients treated with second-generation hormone therapy has never been assessed in a prospective study. This review aims at reviewing what is known about the impact of second-generation hormonotherapy on bone microenvironment.

Management of bone fragility in type 2 diabetes: Perspective from an interdisciplinary expert panel

AimBone fragility is increasingly recognized as a relevant complication of type 2 diabetes (T2D) and diabetic patients with fragility fractures have higher mortality rates than non diabetic individuals or diabetic patients without fractures. However, current diagnostic approaches for fracture risk stratification, such as bone mineral density measurement or the use of risk assessment algorithms, largely underestimate fracture risk in T2D patients. A multidisciplinary expert panel was established in order to in order to formulate clinical consensus recommendations on bone health assessment and management of fracture risk in patients with T2D. Data synthesisThe following key questions were addressed: a) which are the risk factors for bone fragility in T2D?, b) which diagnostic procedures can be currently used to stratify fracture risk in T2D patients?, c) which are the effects of antidiabetic treatments on bone?, and d) how to prevent and treat bone fragility in T2D patients? Based on the available data members of this panel suggest that the stratification of fracture risk in patients with diabetes should firstly rely on the presence of a previous fragility fracture and on the individual risk profile, with the inclusion of T2D-specific risk factors (namely T2D duration above 10 yrs, presence of chronic T2D complications, use of insulin or thiazolidinediones and persistent HbA1c levels above 8% for at least 1 year). Two independent diagnostic approaches were then suggested in the presence or the absence of a prevalent fragility fracture, respectively. ConclusionsClinical trials in T2D patients at risk for fragility fractures are needed to determine the efficacy and safety of available antiresorptive and anabolic agents in this specific setting.

Improved Bone Quality and Bone Healing of Dystrophic Mice by Parabiosis.

Duchenne muscular dystrophy (DMD) is a degenerative muscle disorder characterized by a lack of dystrophin expression in the sarcolemma of muscle fibers. DMD patients acquire bone abnormalities including osteopenia, fragility fractures, and scoliosis indicating a deficiency in skeletal homeostasis. The dKO (dystrophin/Utrophin double knockout) is a more severe mouse model of DMD than the mdx mouse (dystrophin deficient), and display numerous clinically-relevant manifestations, including a spectrum of degenerative changes outside skeletal muscle including bone, articular cartilage, and intervertebral discs. To examine the influence of systemic factors on the bone abnormalities and healing in DMD, parabiotic pairing between dKO mice and mdx mice was established. Notably, heterochronic parabiosis with young mdx mice significantly increased bone mass and improved bone micro-structure in old dKO-hetero mice, which showed progressive bone deterioration. Furthermore, heterochronic parabiosis with WT C56/10J mice significantly improved tibia bone defect healing in dKO-homo mice. These results suggest that systemic blood-borne factor(s) and/or progenitors from WT and young mdx mice can influence the bone deficiencies in dKO mice. Understanding these circulating factors or progenitor cells that are responsible to alleviate the bone abnormalities in dKO mice after heterochronic parabiosis might be useful for the management of poor bone health in DMD.