Quantitative Ultrasound of Phalanx in Primary and Secondary Osteoporosis: Mini-review and Practical Experience

Objective: Dual x-ray absorptiometry (DXA) is gold standard of bone densitometry, but quantitative ultrasound (QUS) of bone is less expensive and portable. This study was designed to assess its usefulness in secondary osteoporosis diagnosis. Materials and Methods: There were 200 secondary osteoporosis cases (rheumatoid arthritis, hemodialysis, kidney transplant patients, and levothyroxine users) and of those, their phalanx QUS results were compared with normal controls. Also, the QUS and DXA results were compared to find any correlation of these methods for diagnosing osteoporosis. Results: There was not significantly different results compared with normal controls, except for those of hemodialysis patients ( P = .00). Also, the comparison of QUS with DXA results showed no significant correlation except in hemodialysis patients, in both spinal and femoral regions ( P = .023 and .21, respectively), as well as the levothyroxine group’s spinal region ( P = .005). Conclusion: These results suggest that QUS of phalanx may be useful in screening secondary osteoporosis but for establishment of diagnosis, DXA measurements are still needed.

Irisin and Secondary Osteoporosis in Humans

Irisin is a peptide secreted by skeletal muscle following exercise that plays an important role in bone metabolism. Numerous experiments in vitro and in mouse models have shown that the administration of recombinant irisin promotes osteogenesis, protects osteocytes from dexamethasone-induced apoptosis, prevents disuse-induced loss of bone and muscle mass, and accelerates fracture healing. Although some aspects still need to be elucidated, such as the dose- and frequency-dependent effects of irisin in cell cultures and mouse models, ample clinical evidence is emerging to support its physiological relevance on bone in humans. A reduction in serum irisin levels, associated with an increased risk of osteoporosis and bone fractures, was observed in postmenopausal women and in both men and women during aging, Recently, cohort studies of subjects with secondary osteoporosis showed that these patients have lower circulating levels of irisin, suggesting that this myokine could be a novel marker to monitor bone quality in this disease. Although there are still few studies, this review discusses the emerging data that are highlighting the involvement of irisin in some diseases that cause secondary osteoporosis.

Pregnancy in a woman with secondary osteoporosis. A case report

BACKGROUND: Glucocorticoid-induced osteoporosis is one of the most serious complications of prolonged (more than three months) systemic glucocorticoid therapy. Rapid bone loss occurs in the first months of treatment, which is a significant risk factor, especially during pregnancy and lactation. When taking systemic glucocorticoid therapy in a daily dose of 5 mg or more (in prednisone equivalent), the relative risk of vertebral fractures increases by 2.9 times. RESULTS: This article examines a clinical case of pregnancy and childbirth of 32-year-old woman diagnosed with secondary complicated osteoporosis during treatment with systemic glucocorticosteroids, who has a history of spine compression fractures during lactation after a previous pregnancy. Vitamin D deficiency was diagnosed and corrected during this pregnancy, which minimized the risk of fractures. A baby was delivered through the birth canal. Bisphosphonate therapy was started six months after birth. No new fractures were diagnosed within two years of observation. CONCLUSIONS: The approach to the management, diagnosis and delivery of pregnant patients with secondary osteoporosis treated long-term with glucocorticosteroids should be multidisciplinary. It is imperative to prescribe vitamin D and calcium preparations throughout pregnancy and lactation.

150 Osteoporosis Risk Factors in Children with Cerebral Palsy

Primary Subject area Complex Care Background Cerebral palsy (CP) is a common motor disability in children. Due to their medical complexity, children with CP are prone to osteoporosis, and consequently, fractures. The prevalence of osteoporosis and its risk factors are poorly understood within this population. Objectives To determine the prevalence and predictors of osteoporosis among a provincial cohort of Canadian children with CP. Design/Methods We performed a retrospective descriptive cohort study in a single Canadian tertiary care pediatric hospital. The medical charts of the 187 children with CP currently followed by the rehabilitation team were reviewed. Primary outcomes were indicators of osteoporosis, including vertebral compression fractures (VCF), long bone fractures and BMD Z-score. Osteoporosis risk factors, including medications, chronic or endocrine disorders linked to secondary osteoporosis, feeding method, and mobilization level (GMFCS), were collected. Two-tail p-values were calculated using the Chi-squared Person’s cumulative test. Results Of the 187 included children, the majority were male (59%) and were living in a rural area (62%). Seven (3.7%) individuals met diagnostic criteria for osteoporosis with a VCF without history of high-energy trauma or local disease. Of these, four were females and three were males. Osteoporosis risk factors are presented in Table 1. GMFCS, feeding method and medications linked to secondary osteoporosis had a significant statistical difference in the children diagnosed with a VCF compared to participants without osteoporosis diagnostic criteria. Conclusion 3.7% of children followed by the provincial rehabilitation team have osteoporosis. This is one of the first studies that establishes the frequency of osteoporosis among a provincial cohort of Canadian children with CP. Mobilization level, feeding method and consumption of medications linked to secondary osteoporosis seem to be major risk factors for osteoporosis in children with CP. Larger prospective studies are needed to confirm this association, in order to improve prevention strategies.

The Roles of TNFRSF11B Genes as a Trigger for Secondary Osteoporosis in Rheumatoid Arthritis Cases

Rheumatoid arthritis (RA) is an autoimmune disorder responsible for widespread and persistent inflammation of the synovial joint lining. Hence, victims are prone to greater risk of developing secondary osteoporosis (OP), a common complication of arthritis. The global prevalence of secondary OP among RA patients is estimated between 22-36%, although certain genetic polymorphisms pose a possible influence. Also, bone remodeling is closely related to the receptor activator nuclear factor-κB ligand (RANKL)/RANK and osteoprotegerin (OPG). The variables play a significant role in osteoclastogenesis, due to the ability of OPG to inhibit osteoclast differentiation and activation. This literature review discusses the relationship of TNFRSF11B gene polymorphisms that encode OPG protein with the risk of developing secondary osteoporosis in RA patients. The research method encompassed exploring similar articles from Pubmed, Cochrane Library, and Medline, using particular keywords, such as “TNFRSF11B polymorphism”, “osteoprotegerin polymorphism”, “rheumatoid arthritis” and “secondary osteoporosis”. Several distinct conclusions were obtained after analyzing the effects of TNFRSF11B gene polymorphisms on secondary OP in RA cases. Furthermore, the TNFRSF11B gene showed various polymorphisms closely related to bone remodeling, including C950T, G1181C, A163G, T245G and rs4876869.

Osteoporotic Hip Fractures in the Elderly: Is there a Gender Difference?

BackgroundOsteoporosis and osteoporotic fracture pose a major public health problem in our aging population. Osteoporotic hip fractures carry an increased morbidity and mortality, with some difference seen between men and women. While overall diagnosis and treatment for osteoporosis have improved, osteoporosis in men remain underdiagnosed and undertreated.AimWe aim to describe the difference in clinical characteristics between elderly men and women with osteoporotic hip fractures in Sarawak General Hospital.MethodsAll patients diagnosed with osteoporotic hip fracture admitted to Sarawak General Hospital from June 2019-March 2021 were recruited and demographic data and clinical features were obtained.ResultsThere were 140 patients with osteoporotic hip fracture, and 40 were men (28.6%). The mean age for males were 74.1 ± 9.5 years, while the mean age for females were 77.4 ± 9.1 years (p=0.06). The types of fracture consisted of neck of femur=78, intertrochanteric=61, and subtrochanteric=1. There were 20 men with secondary osteoporosis (50%), while 13 women (13%) had secondary osteoporosis (p<0.001). The causes of secondary osteoporosis among the men were hypogonadism, COPD, GIOP, renal disease, ADT, thyroid disorder, prostate cancer, and previous gastrectomy. There were two deaths among the men and four deaths among the women during the inpatient and 3 months follow up period. There was no statistical significance between the mortality rates between male patients (5%) and female patients (4%) (p=0.55). ConclusionThere were more females with osteoporotic hip fractures, and there were significantly more males with secondary osteoporotic hip fractures.Trial registration: This study (Male osteoporotic hip fracture in Sarawak General Hospital) was registered with the Malaysian National Medical Research Register (NMRR). Trial registration number: NMRR-19-323-46068 IIR

Secondary Osteoporosis

Osteoporosis is a global public health problem, with fractures contributing to significant morbidity and mortality. Although postmenopausal osteoporosis is most common, up to 30% of postmenopausal women, &gt; 50% of premenopausal women, and between 50% and 80% of men have secondary osteoporosis. Exclusion of secondary causes is important, as treatment of such patients often commences by treating the underlying condition. These are varied but often neglected, ranging from endocrine to chronic inflammatory and genetic conditions. General screening is recommended for all patients with osteoporosis, with advanced investigations reserved for premenopausal women and men aged &lt; 50 years, for older patients in whom classical risk factors for osteoporosis are absent, and for all patients with the lowest bone mass (Z-score ≤ −2). The response of secondary osteoporosis to conventional anti-osteoporosis therapy may be inadequate if the underlying condition is unrecognized and untreated. Bone densitometry, using dual-energy x-ray absorptiometry, may underestimate fracture risk in some chronic diseases, including glucocorticoid-induced osteoporosis, type 2 diabetes, and obesity, and may overestimate fracture risk in others (eg, Turner syndrome). FRAX and trabecular bone score may provide additional information regarding fracture risk in secondary osteoporosis, but their use is limited to adults aged ≥ 40 years and ≥ 50 years, respectively. In addition, FRAX requires adjustment in some chronic conditions, such as glucocorticoid use, type 2 diabetes, and HIV. In most conditions, evidence for antiresorptive or anabolic therapy is limited to increases in bone mass. Current osteoporosis management guidelines also neglect secondary osteoporosis and these existing evidence gaps are discussed.

SENP3-Mediated PPARγ2 DeSUMOylation in BM-MSCs Potentiates Glucocorticoid-Induced Osteoporosis by Promoting Adipogenesis and Weakening Osteogenesis

Glucocorticoid-induced osteoporosis (GIOP) is the most common secondary osteoporosis and reduced bone formation was the main pathological change in GIOP. Our previous studies have shown that there was an imbalance between adipogenic and osteogenic differentiation in GIOP BM-MSCs and peroxisome proliferator-activated receptor γ2 (PPARγ2) played a vital role in this disorders. Here, we reported that there was an increase in ROS level and SENP3 expression in Dex-induced osteoporotic BM-MSCs, and enhanced adipogenesis and weakened osteogenesis in osteoporotic BM-MSCs might be caused by upregulated SENP3. Then we found that SENP3 de-SUMOylated PPARγ2 on K107 site to potentiate adipogenesis and weaken osteogenesis. These results may provide new strategy and target in the clinical diagnosis and treatment of GIOP.

AB0622 WHEN OSTEOPOROSIS, COELIAC DISEASE AND MULTIPLE MYELOMA CO-EXIST

Background:Secondary causes of bone loss are sometimes overlooked in patients who are diagnosed as having osteoporosis. This is especially true if more than one risk factor for secondary osteoporosis is present, with clinicians focusing on the more common cause. Here we present a case of secondary osteoporosis caused by coeliac disease and multiple myeloma.Objectives:Secondary osteoporosis should be suspected in patients with very low bone mineral density and those with no obvious risk factors. Comprehensive examination and investigations must be done to look for all secondary causes because sometimes, as seen in our patient, you may find more than one.Methods:A 74 year old gentleman presented to the rheumatology clinic for assessment of osteoporosis. He had been recently diagnosed with coeliac disease. DXA scan showed a T score of -3.5 at the lumbar spine, -2.5 at the left hip and a low Z score of -2.9. He had not sustained any fractures in the past. There was no history of corticosteroid exposure and no parental history of hip fracture or osteoporosis. He drank up to 21 units of alcohol a week and was an ex-smoker. He was managing a gluten-free diet. His testosterone and vitamin D levels were normal. Serum electrophoresis, done as part of the osteoporosis workup, revealed a diagnosis of multiple myeloma. He then developed back pain and given his new diagnosis of myeloma, prompt investigations were carried out. A skeletal survey showed T7 fracture and a subsequent MRI scan showed impending cord compression, which were treated successfully with radiotherapy. He underwent chemotherapy and autologous stem cell transplantation for his myeloma.He recently had an OGD following one week post gluten rechallenge after an established gluten free diet. His biopsy shows no evidence of coeliac disease. Interestingly, the stem cell transplantation did not only treat our patient’s myeloma, but also his coeliac disease.Results:Z-score is a useful indicator of possible secondary osteoporosis. A score of −2.0 or less is below the expected range for age and should prompt careful scrutiny for an underlying cause.Coeliac disease is a gluten-sensitive enteropathy and a known cause for secondary osteoporosis. It likely causes bone loss by secondary hyperparathyroidism from vitamin D deficiency. Multiple myeloma is a disease of aging adults resulting in osteolytic and/or osteoporotic bone disease through increased bone resorption and decreased bone formation from pro-inflammatory cytokines. While coeliac disease patients are at increased risk of all malignancies, association with multiple myeloma is rare, but has been described.Conclusion:This case highlights the importance of evaluating for secondary causes for low bone mineral density and often, one may find more than one contributory factor. It also shows that a Z-score of −2.0 could help identify patients with a secondary cause for osteoporosis and those who would especially benefit from a thorough history and examination.References:[1]Sahin, Idris & Demir, Cengiz & Alay, Murat & Eminbeyli, Lokman. (2011). The Patient Presenting with Renal Failure Due to Multiple Myeloma Associated with Celiac Disease: Case Report. UHOD - Uluslararasi Hematoloji-Onkoloji Dergisi. 21. 10.4999/uhod.09087.[2]İpek, Belkiz & Aksungar, Fehime & Tiftikci, Arzu & Coskun, Abdurrahman & Serteser, Mustafa & Unsal, Ibrahim. (2016). A rare association: celiac disease and multiple myeloma in an asymptomatic young patient. Turkish Journal of Biochemistry. 41. 10.1515/tjb-2016-0053.[3]Swaminathan K, Flynn R, Garton M, Paterson C, Leese G. Search for secondary osteoporosis: are Z scores useful predictors? Postgrad Med J. 2009 Jan;85(999):38-9. doi: 10.1136/pgmj.2007.065748. PMID: 19240287.Disclosure of Interests:None declared.