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Secondary Osteoporosis and Metabolic Bone Diseases
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Secondary Osteoporosis and Metabolic Bone Diseases

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Orthopedics".

Deadline for manuscript submissions: closed (15 February 2023) | Viewed by 50414

Special Issue Editor

Prof. Dr. Amr El-Husseini

E-Mail Website
Guest Editor
Professor and Medical Director, Division of Nephrology, Bone and Mineral Metabolism, University of Kentucky, Lexington, KY, USA
Interests: metabolic bone disordes; osteoporosis

Special Issue Information

Dear Colleagues,

There is ample evidence that patients with various organ dysfunction have an increased risk of bone fragility and fractures. Osteoporosis is not only influenced by low bone volume and mass but also by poor microarchitecture and tissue quality. More emphasis has been given to the quantitative rather than qualitative assessment of bone health, both in primary and secondary osteoporosis. Bone mineral density (BMD) is an incredibly useful clinical tool in assessing bone strength, but it may underestimate the fracture risk in patients with secondary osteoporosis. Serum and urinary bone biomarkers have been found to be reflective of bone activities and predictive of fractures independently of BMD. By utilizing new technologies such as innovative biomarkers and high-resolution images, we can better assess the bone health and fracture risk. Moreover, invasive assessments such as bone histology and micro-indentation are great counterparts.

Various bone medications build up bone mass but also affect tissue quality. Anti-resorptive therapies strikingly reduce bone turnover; however, they can impair bone mineralization and negatively affect the micro-damage repair and causing upsurge bone brittleness. On the other hand, some osteoporosis therapies may cause redistribution of bone structure that may improve bone strength without a noticeable effect on BMD. This may explain why some drugs can affect fracture risk disproportionately to changes in BMD.

This issue focuses on the current and future directions of bone health and management in patients with secondary osteoporosis and various metabolic bone diseases.

Prof. Dr. Amr El-Husseini
Guest Editor

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Keywords

  • Osteoporosis
  • Metabolic bone disorders
  • Fractures
  • Bone loss
  • Organ dysfunction

Published Papers (15 papers)

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Research

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10 pages, 971 KiB  
Article
Bone Turnover Markers and Bone Mineral Density in Children with Hypophosphatemic Rickets
by Izabela Michałus, Anna Łupińska, Izabela Woch, Katarzyna Wieczorek-Szukała, Danuta Chlebna-Sokół and Andrzej Lewiński
J. Clin. Med. 2022, 11(15), 4622; https://doi.org/10.3390/jcm11154622 - 8 Aug 2022
Viewed by 1408
Abstract
Hypophosphatemic rickets is a rare disease that results in bone deformities. However, little is known about bone turnover and bone mass disorders in this disease. This retrospective study included 12 children aged 1–16 years diagnosed with hypophosphatemic rickets. Parameters of calcium-phosphate metabolism and [...] Read more.
Hypophosphatemic rickets is a rare disease that results in bone deformities. However, little is known about bone turnover and bone mass disorders in this disease. This retrospective study included 12 children aged 1–16 years diagnosed with hypophosphatemic rickets. Parameters of calcium-phosphate metabolism and bone turnover markers were analysed. Bone mineral density was assessed with the use of dual-energy X-ray absorptiometry, and indices of quantitative ultrasound examination of tibiae and radial bones were analysed. In the majority of patients, hypophosphatemia and hyperphosphaturia were present. The assessed bone turnover markers showed increased bone formation. Increased pyridinoline levels were found in 5 out of 12 patients. Bone mineral density was decreased only in one patient. Decreased values of quantitative ultrasound examination were observed in all the analysed patients. Conclusions: (1) Bone metabolism disturbances, reflected in the increased values of bone turnover markers and worse bone quality, were found in the group of patients with hypophosphatemic rickets. (2) It is crucial to determine bone turnover markers, dual-energy X-ray absorptiometry findings and indices of quantitative ultrasound examination in order to monitor progress of the disease, as well as treatment effects. Full article
(This article belongs to the Special Issue Secondary Osteoporosis and Metabolic Bone Diseases)
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13 pages, 654 KiB  
Article
Prevalence and Factors of Osteoporosis and High Risk of Osteoporotic Fracture in Patients with Ankylosing Spondylitis: A Multicenter Comparative Study of Bone Mineral Density and the Fracture Risk Assessment Tool
by Ji-Won Kim, Sunghoon Park, Ju-Yang Jung, Hyoun-Ah Kim, Seong-Ryul Kwon, Sang Tae Choi, Sung-Soo Kim, Sang-Hyeon Kim and Chang-Hee Suh
J. Clin. Med. 2022, 11(10), 2830; https://doi.org/10.3390/jcm11102830 - 17 May 2022
Cited by 8 | Viewed by 2260
Abstract
Background: We investigated the prevalence of and the factors associated with a high risk of osteoporotic fractures in Korean patients with ankylosing spondylitis (AS). Methods: This was a multicenter, retrospective study including 219 AS patients from five university hospitals; the control group was [...] Read more.
Background: We investigated the prevalence of and the factors associated with a high risk of osteoporotic fractures in Korean patients with ankylosing spondylitis (AS). Methods: This was a multicenter, retrospective study including 219 AS patients from five university hospitals; the control group was selected by matching age and sex with those of the AS patients. The fracture risk was evaluated based on bone mineral density (BMD) measured by dual-energy X-ray absorptiometry and the fracture risk assessment tool (FRAX) with/without BMD. Results: The mean age of the patients was 47.6 years, and 144 (65.8%) patients were men. According to the WHO criteria and FRAX with/without BMD, the candidates for pharmacological treatment were 44 (20.1%), 20 (13.2%), and 23 (15.1%) patients, respectively, significantly more than those in the healthy control group. Among them, the proportion of patients receiving osteoporosis treatment was 39.1–75%. In logistic regression analysis, menopause was an independent factor for the high risk of fracture according to the WHO criteria and FRAX with/without BMD. C-reactive protein level (odds ratio (OR) 3.8 and OR 6) and glucocorticoid use (OR 1.5 and OR 1.7) were associated with a high risk of osteoporotic fracture based on FRAX without BMD and osteoporosis diagnosed according to the WHO criteria. Conclusions: Our study suggests that both FRAX and WHO criteria may be complementary for treatment decisions to reduce osteoporotic fractures in patients with AS. Full article
(This article belongs to the Special Issue Secondary Osteoporosis and Metabolic Bone Diseases)
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10 pages, 965 KiB  
Article
Machine Learning Algorithms: Prediction and Feature Selection for Clinical Refracture after Surgically Treated Fragility Fracture
by Hirokazu Shimizu, Ken Enda, Tomohiro Shimizu, Yusuke Ishida, Hotaka Ishizu, Koki Ise, Shinya Tanaka and Norimasa Iwasaki
J. Clin. Med. 2022, 11(7), 2021; https://doi.org/10.3390/jcm11072021 - 5 Apr 2022
Cited by 3 | Viewed by 1925
Abstract
Background: The number of patients with fragility fracture has been increasing. Although the increasing number of patients with fragility fracture increased the rate of fracture (refracture), the causes of refracture are multifactorial, and its predictors are still not clarified. In this issue, we [...] Read more.
Background: The number of patients with fragility fracture has been increasing. Although the increasing number of patients with fragility fracture increased the rate of fracture (refracture), the causes of refracture are multifactorial, and its predictors are still not clarified. In this issue, we collected a registry-based longitudinal dataset that contained more than 7000 patients with fragility fractures treated surgically to detect potential predictors for clinical refracture. Methods: Based on the fact that machine learning algorithms are often used for the analysis of a large-scale dataset, we developed automatic prediction models and clarified the relevant features for patients with clinical refracture. Formats of input data containing perioperative clinical information were table data. Clinical refracture was documented as the primary outcome if the diagnosis of fracture was made at postoperative outpatient care. A decision-tree-based model, LightGBM, had moderate accuracy for the prediction in the test and the independent dataset, whereas the other models had poor accuracy or worse. Results: From a clinical perspective, rheumatoid arthritis (RA) and chronic kidney disease (CKD) were noted as the relevant features for patients with clinical refracture, both of which were associated with secondary osteoporosis. Conclusion: The decision-tree-based algorithm showed the precise prediction of clinical refracture, in which RA and CKD were detected as the potential predictors. Understanding these predictors may improve the management of patients with fragility fractures. Full article
(This article belongs to the Special Issue Secondary Osteoporosis and Metabolic Bone Diseases)
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14 pages, 1266 KiB  
Communication
Could Bone Biomarkers Predict Bone Turnover after Kidney Transplantation?—A Proof-of-Concept Study
by Juliana Magalhães, Janete Quelhas-Santos, Luciano Pereira, Ricardo Neto, Inês Castro-Ferreira, Sandra Martins, João Miguel Frazão and Catarina Carvalho
J. Clin. Med. 2022, 11(2), 457; https://doi.org/10.3390/jcm11020457 - 17 Jan 2022
Cited by 1 | Viewed by 1971
Abstract
Aim: Bone disease after kidney transplant (KT) results from multiple factors, including previous bone and mineral metabolism disturbances and effects of transplant-related medications. New biomolecules have been recently associated with the development and progression of the chronic kidney disease–associated bone and mineral disorder [...] Read more.
Aim: Bone disease after kidney transplant (KT) results from multiple factors, including previous bone and mineral metabolism disturbances and effects of transplant-related medications. New biomolecules have been recently associated with the development and progression of the chronic kidney disease–associated bone and mineral disorder (CKD-MBD). These include sclerostin and the soluble receptor activator of nuclear factor-kB ligand (sRANKL). Methods: To better understand the role of biomarkers in post-transplant bone disease, this study was designed to prospectively evaluate and correlate results from the histomorphometric analysis of bone biopsies after KT with emerging serum biomarkers of the CKD-MBD: sclerostin, Dickkopf-related protein 1 (Dkk-1), sRANKL and osteo-protegerin (OPG). Results: Our data shows a significant increase in plasma levels of bioactive sclerostin after KT accompanied by a significant reduction in plasma levels of Dkk-1, suggesting a promotion of the inhibition of bone formation by osteoblasts through the activation of these inhibitors of the Wnt signaling pathway. In addition, we found a significant increase in plasma levels of free sRANKL after KT accompanied by a significant reduction in plasma levels of its decoy receptor OPG, suggesting an enhanced bone resorption by osteoclasts mediated by this mechanism. Conclusions: Taken together, these results suggest that the loss of bone volume observed after KT could be explain mainly by the inhibition of bone formation mediated by sclerostin accompanied by an enhanced bone resorption mediated by sRANKL. Full article
(This article belongs to the Special Issue Secondary Osteoporosis and Metabolic Bone Diseases)
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10 pages, 1007 KiB  
Article
Bone Mineral Density Compared to Trabecular Bone Score in Primary Hyperparathyroidism
by Alicia R. Jones, Koen Simons, Susan Harvey and Vivian Grill
J. Clin. Med. 2022, 11(2), 330; https://doi.org/10.3390/jcm11020330 - 10 Jan 2022
Cited by 6 | Viewed by 1446
Abstract
Individuals with primary hyperparathyroidism (PHPT) have reduced bone mineral density (BMD) according to dual X-ray absorptiometry at cortical sites, with relative sparing of trabecular BMD. However, fracture risk is increased at all sites. Trabecular bone score (TBS) may more accurately describe their bone [...] Read more.
Individuals with primary hyperparathyroidism (PHPT) have reduced bone mineral density (BMD) according to dual X-ray absorptiometry at cortical sites, with relative sparing of trabecular BMD. However, fracture risk is increased at all sites. Trabecular bone score (TBS) may more accurately describe their bone quality and fracture risk. This study compared how BMD and TBS describe bone quality in PHPT. We conducted a retrospective cross-sectional study with a longitudinal component, of adults with PHPT, admitted to a tertiary hospital in Australia over ten years. The primary outcome was the TBS at the lumbar spine, compared to BMD, to describe bone quality and predict fractures. Secondary outcomes compared changes in TBS after parathyroidectomy. Of 68 included individuals, the mean age was 65.3 years, and 79% were female. Mean ± SD T-scores were −1.51 ± 1.63 at lumbar spine and mean TBS was 1.19 ± 0.12. Only 20.6% of individuals had lumbar spine BMD indicative of osteoporosis, while 57.4% of TBS were ≤1.20, indicating degraded architecture. There was a trend towards improved fracture prediction using TBS compared to BMD which did not reach statistical significance. Comparison of 15 individuals following parathyroidectomy showed no improvement in TBS. Full article
(This article belongs to the Special Issue Secondary Osteoporosis and Metabolic Bone Diseases)
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20 pages, 5165 KiB  
Article
Structural Changes in Trabecular Bone, Cortical Bone and Hyaline Cartilage as Well as Disturbances in Bone Metabolism and Mineralization in an Animal Model of Secondary Osteoporosis in Clostridium perfringens Infection
by Agnieszka Tomczyk-Warunek, Tomasz Blicharski, Siemowit Muszyński, Ewa Tomaszewska, Piotr Dobrowolski, Rudolf Blicharski, Jaromir Jarecki, Anna Arczewska-Włosek, Sylwester Świątkiewicz and Damian Józefiak
J. Clin. Med. 2022, 11(1), 205; https://doi.org/10.3390/jcm11010205 - 30 Dec 2021
Cited by 2 | Viewed by 1937
Abstract
There is no information regarding whether changes in the microbiological balance of the gastrointestinal tract as a result of an infection with Clostridium perfringens influence the development of metabolic bone disorders. The experiment was carried out on male broiler chickens divided into two [...] Read more.
There is no information regarding whether changes in the microbiological balance of the gastrointestinal tract as a result of an infection with Clostridium perfringens influence the development of metabolic bone disorders. The experiment was carried out on male broiler chickens divided into two groups: control (n = 10) and experimental (n = 10). The experimental animals were infected with Clostridium perfringens between 17 and 20 days of age. The animals were euthanized at 42 days of age. The structural parameters of the trabecular bone, cortical bone, and hyaline cartilage as well as the mineralization of the bone were determined. The metabolism of the skeletal system was assessed by determining the levels of bone turnover markers, hormones, and minerals in the blood serum. The results confirm that the disturbed composition of the gastrointestinal microflora has an impact on the mineralization and metabolism of bone tissue, leading to the structural changes in cortical bone, trabecular bone, and hyaline cartilage. On the basis of the obtained results, it can be concluded that changes in the microenvironment of the gastrointestinal tract by infection with C. perfringens may have an impact on the earlier development of osteoporosis. Full article
(This article belongs to the Special Issue Secondary Osteoporosis and Metabolic Bone Diseases)
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24 pages, 13030 KiB  
Article
Femoral µCT Analysis, Mechanical Testing and Immunolocalization of Bone Proteins in β-Hydroxy β-Methylbutyrate (HMB) Supplemented Spiny Mouse in a Model of Pregnancy and Lactation-Associated Osteoporosis
by Ewa Tomaszewska, Siemowit Muszyński, Janine Donaldson, Piotr Dobrowolski, Deepesh K. P. Chand, Agnieszka Tomczyk-Warunek, Monika Hułas-Stasiak, Iwona Puzio, Krzysztof Lamorski, Cezary Sławiński, Mirosław Jabłoński and Tomasz Blicharski
J. Clin. Med. 2021, 10(21), 4808; https://doi.org/10.3390/jcm10214808 - 20 Oct 2021
Cited by 1 | Viewed by 2447
Abstract
A metabolite of leucine, ß-hydroxy-ß-methylbutyrate (HMB), used as a dietary supplement effects muscle tissue gain and bone tissue quality. Since there are no studies on the effects of HMB during pregnancy yet, the aim of the current study was to determine the effects [...] Read more.
A metabolite of leucine, ß-hydroxy-ß-methylbutyrate (HMB), used as a dietary supplement effects muscle tissue gain and bone tissue quality. Since there are no studies on the effects of HMB during pregnancy yet, the aim of the current study was to determine the effects of HMB supplementation during pregnancy on osteoporotic bone quality postpartum and post-lactation using spiny mice (Acomys cahirinus) as the animal models. The six-month-old dams were divided into four groups: pregnant and lactating controls, and pregnant and lactating HMB-treated (during the second trimester of pregnancy) females. The intensity of the immunoreaction of osteocalcin (OC), osteoprotegerin (OPG), bone morphogenetic protein 2 (BMP-2), tissue inhibitor of metalloproteinases 2 (TIMP-2), matrix metalloproteinase 8 and 13 (MMP-8 and MMP-13) and proteins involved in bone turnover, was measured in femoral trabecular and compact bone, as well as in the hyaline and epiphyseal cartilage of the femora. The analysis of the trabecular bone microarchitecture showed that the administration of HMB to pregnant females, by influencing the proteins responsible for bone cell activity and collagen remodeling, can provide protection from bone loss. Based on the results of the current study it can be assumed that HMB administration to pregnant females has a more positive impact on trabecular than compact bone. Full article
(This article belongs to the Special Issue Secondary Osteoporosis and Metabolic Bone Diseases)
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12 pages, 1969 KiB  
Article
The Risk of Developing Osteoporosis in Hemolytic Anemia—What Aggravates the Bone Loss?
by Leiyu Shi, Cheng-Li Lin, Ching-Huang Su, Keng-Chian Lin, Kam-Hang Leong, Yu-Ting Tina Wang, Chien-Feng Kuo and Shin-Yi Tsai
J. Clin. Med. 2021, 10(15), 3364; https://doi.org/10.3390/jcm10153364 - 29 Jul 2021
Cited by 5 | Viewed by 2345
Abstract
Hemolytic anemia (HA) renders erythropoietic stress on the bone marrow and has been linked to osteoporosis. In this nationwide retrospective cohort study, we examined this correlation by utilizing the Taiwan National Health Insurance Research Database (NHIRD). We identified two cohorts, matching population with [...] Read more.
Hemolytic anemia (HA) renders erythropoietic stress on the bone marrow and has been linked to osteoporosis. In this nationwide retrospective cohort study, we examined this correlation by utilizing the Taiwan National Health Insurance Research Database (NHIRD). We identified two cohorts, matching population with and without HA in a 1:4 ratio. A total of 2242 HA patients and 8968 non-HA patients were enrolled. Patients with HA had a significantly higher cumulative incidence (log-rank test p = 0.0073), higher incidence density (5.11 vs. 3.76 per 1000 persons-years), and a 1.31-fold risk of developing osteoporosis than non-HA patients (aHR = 1.31, 95% C.I. 1.04–1.63, p = 0.01). After adjusting for age, sex, and comorbidities, patients with factors including female (aHR = 2.57, 95% C.I. 2.05–3.22, p < 0.001), age > 65 (aHR = 9.25, 95% C.I. 7.46–11.50, p < 0.001), diagnosis of cholelithiasis (aHR = 1.76, 95% C.I. 1.20–2.58, p = 0.003) and peptic ulcer disease (aHR = 1.87, 95% C.I. 1.52–2.29, p < 0.001) had significantly higher risk of osteoporosis. We propose that this correlation may be related to increased hematopoietic stress, increased consumption of nitric oxide (NO) by hemolysis, and the inhibitory effects of iron supplements on osteogenesis through the receptor activator of nuclear factor κB ligand (RANKL)/Osteoprotegerin pathway and the Runt-related transcription factor 2 (RUNX2) factor. Our findings suggest that patients with hemolytic anemia are at a higher risk of developing osteoporosis, and it would be in the patient’s best interest for physicians to be aware of this potential complication and offer preventative measures. Full article
(This article belongs to the Special Issue Secondary Osteoporosis and Metabolic Bone Diseases)
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Review

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24 pages, 487 KiB  
Review
Is Adynamic Bone Always a Disease? Lessons from Patients with Chronic Kidney Disease
by Eman Nagy, Mahmoud M. Sobh, Mohamed Abdalbary, Sherouk Elnagar, Rabab Elrefaey, Shimaa Shabaka, Nehal Elshabrawy, Rasha Shemies, Mona Tawfik, Cássia Gomes S. Santos, Fellype C. Barreto and Amr El-Husseini
J. Clin. Med. 2022, 11(23), 7130; https://doi.org/10.3390/jcm11237130 - 30 Nov 2022
Cited by 3 | Viewed by 4065
Abstract
Renal osteodystrophy (ROD) is a common complication of end-stage kidney disease that often starts early with loss of kidney function, and it is considered an integral part in management of patients with chronic kidney disease (CKD). Adynamic bone (ADB) is characterized by suppressed [...] Read more.
Renal osteodystrophy (ROD) is a common complication of end-stage kidney disease that often starts early with loss of kidney function, and it is considered an integral part in management of patients with chronic kidney disease (CKD). Adynamic bone (ADB) is characterized by suppressed bone formation, low cellularity, and thin osteoid seams. There is accumulating evidence supporting increasing prevalence of ADB, particularly in early CKD. Contemporarily, it is not very clear whether it represents a true disease, an adaptive mechanism to prevent bone resorption, or just a transitional stage. Several co-players are incriminated in its pathogenesis, such as age, diabetes mellitus, malnutrition, uremic milieu, and iatrogenic factors. In the present review, we will discuss the up-to-date knowledge of the ADB and focus on its impact on bone health, fracture risk, vascular calcification, and long-term survival. Moreover, we will emphasize the proper preventive and management strategies of ADB that are pivotal issues in managing patients with CKD. It is still unclear whether ADB is always a pathologic condition or whether it can represent an adaptive process to suppress bone resorption and further bone loss. In this article, we tried to discuss this hard topic based on the available limited information in patients with CKD. More studies are needed to be able to clearly address this frequent ROD finding. Full article
(This article belongs to the Special Issue Secondary Osteoporosis and Metabolic Bone Diseases)
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13 pages, 3744 KiB  
Review
A Systematic Review and Meta-Analysis on Metabolic Bone Disease in Patients with Primary Sclerosing Cholangitis
by Claudiu Marinel Ionele, Adina Turcu-Stiolica, Mihaela Simona Subtirelu, Bogdan Silviu Ungureanu, George Ovidiu Cioroianu and Ion Rogoveanu
J. Clin. Med. 2022, 11(13), 3807; https://doi.org/10.3390/jcm11133807 - 30 Jun 2022
Cited by 5 | Viewed by 1639
Abstract
Data about the association between primary sclerosing cholangitis (PSC) and metabolic bone disease are still unclear. PSC is a chronic cholestatic liver disease (CCLD) which affects the biliary tract, and it has a highly variable natural history. We systematically searched until 28 February [...] Read more.
Data about the association between primary sclerosing cholangitis (PSC) and metabolic bone disease are still unclear. PSC is a chronic cholestatic liver disease (CCLD) which affects the biliary tract, and it has a highly variable natural history. We systematically searched until 28 February 2022 MEDLINE, Cochrane Central Register of Controlled Trials, the ISI Web of Science, and SCOPUS, for studies in patients with PSC. We identified 343 references to potential studies. After screening them, we included eight studies (893 PSC patients, 398 primary biliary cirrhosis (PBC) patients, and 673 healthy controls) for the present meta-analysis. Pooled analyses found no difference in BMD-LS (Z = 0.02, p-value = 0.98) between PSC patients and healthy controls. BMD-LS was statistically lower in PBC patients than in PSC patients (Mean Difference, MD, 0.06, 95% CI 0.03 to 0.09, p-value = 0.0007). The lumbar spine T-score was higher in the PSC patients compared with PBC patients (MD 0.23, 95% CI 0.04 to 0.42, p-value = 0.02). Given the limited literature available, better designed, and larger scale primary studies will be required to confirm our conclusion. Full article
(This article belongs to the Special Issue Secondary Osteoporosis and Metabolic Bone Diseases)
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12 pages, 294 KiB  
Review
Osteosarcopenia—The Role of Dual-Energy X-ray Absorptiometry (DXA) in Diagnostics
by Aleksandra Gonera-Furman, Marek Bolanowski and Diana Jędrzejuk
J. Clin. Med. 2022, 11(9), 2522; https://doi.org/10.3390/jcm11092522 - 30 Apr 2022
Cited by 8 | Viewed by 2829
Abstract
Osteoporosis and sarcopenia lead to increased mortality, but their early diagnosis allows preventive measures and treatment to be implemented. The dual-energy X-ray absorptiometry (DXA) method enables the assessment of both bone mineral density (BMD) and bone quality based on the trabecular bone score [...] Read more.
Osteoporosis and sarcopenia lead to increased mortality, but their early diagnosis allows preventive measures and treatment to be implemented. The dual-energy X-ray absorptiometry (DXA) method enables the assessment of both bone mineral density (BMD) and bone quality based on the trabecular bone score (TBS), the Bone Strain Index (BSI), hip structure analysis (HSA), and comprehensive hip axis length (HAL). The main complications of osteoporosis are fractures, and a BMD value or T-score together with TBS can be also applied in fracture risk calculation using the Fracture Risk Assessment Tool (FRAX). In recent years, the interest in sarcopenia has increased. There are many methods for assessing the quality, quantity and function of muscles. Total body DXA provides information not only about the BMD of the whole skeleton or the amount of lean tissue (identified as fat-free mass), but also about the amount and distribution of adipose tissue. Some parameters obtained from DXA measurements related to muscle and/or fat mass are used in the assessment of osteosarcopenia. The following article presents a wide range of possibilities for the use of the DXA method in the diagnosis of osteosarcopenia because DXA is a useful technique for the diagnosis of bone density and body composition together. Full article
(This article belongs to the Special Issue Secondary Osteoporosis and Metabolic Bone Diseases)
36 pages, 3770 KiB  
Review
Secondary Osteoporosis and Metabolic Bone Diseases
by Mahmoud M. Sobh, Mohamed Abdalbary, Sherouk Elnagar, Eman Nagy, Nehal Elshabrawy, Mostafa Abdelsalam, Kamyar Asadipooya and Amr El-Husseini
J. Clin. Med. 2022, 11(9), 2382; https://doi.org/10.3390/jcm11092382 - 24 Apr 2022
Cited by 30 | Viewed by 17334
Abstract
Fragility fracture is a worldwide problem and a main cause of disability and impaired quality of life. It is primarily caused by osteoporosis, characterized by impaired bone quantity and or quality. Proper diagnosis of osteoporosis is essential for prevention of fragility fractures. Osteoporosis [...] Read more.
Fragility fracture is a worldwide problem and a main cause of disability and impaired quality of life. It is primarily caused by osteoporosis, characterized by impaired bone quantity and or quality. Proper diagnosis of osteoporosis is essential for prevention of fragility fractures. Osteoporosis can be primary in postmenopausal women because of estrogen deficiency. Secondary forms of osteoporosis are not uncommon in both men and women. Most systemic illnesses and organ dysfunction can lead to osteoporosis. The kidney plays a crucial role in maintaining physiological bone homeostasis by controlling minerals, electrolytes, acid-base, vitamin D and parathyroid function. Chronic kidney disease with its uremic milieu disturbs this balance, leading to renal osteodystrophy. Diabetes mellitus represents the most common secondary cause of osteoporosis. Thyroid and parathyroid disorders can dysregulate the osteoblast/osteoclast functions. Gastrointestinal disorders, malnutrition and malabsorption can result in mineral and vitamin D deficiencies and bone loss. Patients with chronic liver disease have a higher risk of fracture due to hepatic osteodystrophy. Proinflammatory cytokines in infectious, autoimmune, and hematological disorders can stimulate osteoclastogenesis, leading to osteoporosis. Moreover, drug-induced osteoporosis is not uncommon. In this review, we focus on causes, pathogenesis, and management of secondary osteoporosis. Full article
(This article belongs to the Special Issue Secondary Osteoporosis and Metabolic Bone Diseases)
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14 pages, 304 KiB  
Review
Personalized Therapeutic Strategies in the Management of Osteoporosis in Patients with Autoantibody-Positive Rheumatoid Arthritis
by Bernardo D’Onofrio, Michele di Lernia, Ludovico De Stefano, Serena Bugatti, Carlomaurizio Montecucco and Laura Bogliolo
J. Clin. Med. 2022, 11(9), 2341; https://doi.org/10.3390/jcm11092341 - 22 Apr 2022
Cited by 3 | Viewed by 2023
Abstract
Bone mineral density (BMD) reduction and fragility fractures still represent a major source of morbidity in rheumatoid arthritis (RA) patients, despite adequate control of the disease. An increasing number of clinical and experimental evidence supports the role of autoantibodies, especially anti-citrullinated protein antibodies [...] Read more.
Bone mineral density (BMD) reduction and fragility fractures still represent a major source of morbidity in rheumatoid arthritis (RA) patients, despite adequate control of the disease. An increasing number of clinical and experimental evidence supports the role of autoantibodies, especially anti-citrullinated protein antibodies (ACPAs), in causing localized and generalised bone loss in ways that are both dependent on and independent of inflammation and disease activity. The human receptor activator of nuclear factor kappa B and its ligand—the so-called RANK-RANKL pathway—is known to play a key role in promoting osteoclasts’ activation and bone depletion, and RANKL levels were shown to be higher in ACPA-positive early untreated RA patients. Thus, ACPA-positivity can be considered a specific risk factor for systemic and periarticular bone loss. Through the inhibition of the RANK-RANKL system, denosumab is the only antiresorptive drug currently available that exhibits both a systemic anti-osteoporotic activity and a disease-modifying effect when combined with conventional synthetic or biologic disease-modifying anti-rheumatic drugs (DMARDs). Thus, the combination of DMARD and anti-RANKL therapy could be beneficial in the prevention of fragility fractures and structural damage in the subset of RA patients at risk of radiographic progression, as in the presence of ACPAs. Full article
(This article belongs to the Special Issue Secondary Osteoporosis and Metabolic Bone Diseases)
13 pages, 921 KiB  
Review
The Bone Strain Index: An Innovative Dual X-ray Absorptiometry Bone Strength Index and Its Helpfulness in Clinical Medicine
by Fabio Massimo Ulivieri and Luca Rinaudo
J. Clin. Med. 2022, 11(9), 2284; https://doi.org/10.3390/jcm11092284 - 20 Apr 2022
Cited by 13 | Viewed by 2873
Abstract
Bone strain Index (BSI) is an innovative index of bone strength that provides information about skeletal resistance to loads not considered by existing indexes (Bone Mineral Density, BMD. Trabecular Bone Score, TBS. Hip Structural Analysis, HSA. Hip Axis Length, HAL), and, thus, improves [...] Read more.
Bone strain Index (BSI) is an innovative index of bone strength that provides information about skeletal resistance to loads not considered by existing indexes (Bone Mineral Density, BMD. Trabecular Bone Score, TBS. Hip Structural Analysis, HSA. Hip Axis Length, HAL), and, thus, improves the predictability of fragility fractures in osteoporotic patients. This improved predictability of fracture facilitates the possibility of timely intervention with appropriate therapies to reduce the risk of fracture. The development of the index was the result of combining clinical, radiographical and construction-engineering skills. In fact, from a physical point of view, primary and secondary osteoporosis, leading to bone fracture, are determined by an impairment of the physical properties of bone strength: density, internal structure, deformation and fatigue. Dual X-ray absorptiometry (DXA) is the gold standard for assessing bone properties, and it allows measurement of the BMD, which is reduced mainly in primary osteoporosis, the structural texture TBS, which can be particularly degraded in secondary osteoporosis, and the bone geometry (HSA, HAL). The authors recently conceived and developed a new bone deformation index named Bone Strain Index (BSI) that assesses the resistance of bone to loads. If the skeletal structure is equated to engineering construction, these three indexes are all considered to determine the load resistance of the construct. In particular, BSI allows clinicians to detect critical information that BMD and TBS cannot explain, and this information is essential for an accurate definition of a patient’s fracture risk. The literature demonstrates that both lumbar and femoral BSI discriminate fractured osteoporotic people, that they predict the first fragility fracture, and further fragility fractures, monitor anabolic treatment efficacy and detect patients affected by secondary osteoporosis. BSI is a new diagnostic tool that offers a unique perspective to clinical medicine to identify patients affected by primary and, specially, secondary osteoporosis. This literature review illustrates BSI’s state of the art and its ratio in clinical medicine. Full article
(This article belongs to the Special Issue Secondary Osteoporosis and Metabolic Bone Diseases)
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Case Report
Hajdu-Cheney Syndrome: A Novel NOTCH2 Mutation in a Spanish Child in Treatment with Vibrotherapy: A Case Report
by Jonathan Cortés-Martín, Lourdes Díaz-Rodríguez, Beatriz Piqueras-Sola, Juan Carlos Sánchez-García, Antonio Liñán González and Raquel Rodríguez-Blanque
J. Clin. Med. 2022, 11(17), 5205; https://doi.org/10.3390/jcm11175205 - 2 Sep 2022
Cited by 2 | Viewed by 2133
Abstract
A case report of an 11-year-old boy with a de novo variant in NOTCH2 and clinical features characteristic of Hajdu-Cheney syndrome is reported, with acroosteolysis of the distal phalanges of the feet and hands, generalized osteoporosis, musculoskeletal and craniofacial alterations, short stature, bowing [...] Read more.
A case report of an 11-year-old boy with a de novo variant in NOTCH2 and clinical features characteristic of Hajdu-Cheney syndrome is reported, with acroosteolysis of the distal phalanges of the feet and hands, generalized osteoporosis, musculoskeletal and craniofacial alterations, short stature, bowing of long bones, vertebral anomalies, genu recurvatum, hypertrichosis, joint and skin hyperlaxity, atopic dermatitis, megalocorneas, micrognathia and frequent respiratory infections, among others. Treatment is with bisphosphonates in the framework of bone density improvement and with focal vibration therapy for rehabilitation of the musculoskeletal system and gait improvement. The three generalities of this pathology—phenotypic variability, degenerative character and the presence of generalized osteoporosis and acroosteolysis of the distal phalanges—are seen in this case, whose diagnostic confirmation was made by genetic study. Full article
(This article belongs to the Special Issue Secondary Osteoporosis and Metabolic Bone Diseases)
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