Frailty, Sarcopenia and Osteoporosis. / Fragilidad, sarcopenia y osteoporosis.

Frailty, sarcopenia and osteoporosis are entities specific to the elderly, who share some risk factors. For this reason, their relationship has been studied in different works, which have provided disparate results, probably because these studies have not always focused on the same aspects. This article reviews the relationship of frailty and sarcopenia with osteoporosis.

Long-Term Treatment and Effect of Discontinuation of Calcifediol in Postmenopausal Women with Vitamin D Deficiency: A Randomized Trial.

Vitamin D plays a major role in bone health and probably also in multiple extraskeletal acute and chronic diseases. Although supplementation with calcifediol, a vitamin D metabolite, has demonstrated efficacy and safety in short-term clinical trials, its effects after long-term monthly administration have been studied less extensively. This report describes the results of a 1-year, phase III-IV, double-blind, randomized, controlled, parallel, multicenter superiority clinical trial to assess the efficacy and safety of monthly calcifediol 0.266 mg versus cholecalciferol 25,000 IU (0.625 mg) in postmenopausal women with vitamin D deficiency (25(OH)D < 20 ng/mL). A total of 303 women were randomized and 298 evaluated. Patients were randomized 1:1:1 to calcifediol 0.266 mg/month for 12 months (Group A1), calcifediol 0.266 mg/month for 4 months followed by placebo for 8 months (Group A2), and cholecalciferol 25,000 IU/month (0.625 mg/month) for 12 months (Group B). By month 4, stable 25(OH)D levels were documented with both calcifediol and cholecalciferol (intention-to-treat population): 26.8 ± 8.5 ng/mL (Group A1) and 23.1 ± 5.4 ng/mL (Group B). By month 12, 25(OH)D levels were 23.9 ± 8.0 ng/mL (Group A1) and 22.4 ± 5.5 ng/mL (Group B). When calcifediol treatment was withdrawn in Group A2, 25(OH)D levels decreased to baseline levels (28.5 ± 8.7 ng/mL at month 4 versus 14.4 ± 6.0 ng/mL at month 12). No relevant treatment-related safety issues were reported in any of the groups. The results confirm that long-term treatment with monthly calcifediol in vitamin D-deficient patients is effective and safe. The withdrawal of treatment leads to a pronounced decrease of 25(OH)D levels. Calcifediol presented a faster onset of action compared to monthly cholecalciferol. Long-term treatment produces stable and sustained 25(OH)D concentrations with no associated safety concerns. © 2023 Faes Farma SA. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Aminobisphosphonates: Reconsideration 25 years after their approval for the treatment of osteoporosis. / Aminobisfosfonatos: reconsideración a los 25 años de su aprobación para el tratamiento de la osteoporosis.

Aminobisphosphonates are widely used in the treatment of osteoporosis. They have a high affinity for hydroxyapatite, binding primarily to resorbing surfaces, but also to forming surfaces and to some extent to resting surfaces. They inhibit osteoclasts, thereby decreasing remodelling units. Consequently, they increase bone mass and reduce stress risers. This decreases the risk of fractures. If this decrease is sufficient, they can be temporarily withdrawn (drug holidays), which prevents serious complications (atypical femoral fracture). They probably reduce mortality. Virtually all patients with osteoporosis can benefit from them at some point in the course of their disease (at the beginning of treatment or after the administration of anabolics, selective estrogen receptor modulators or denosumab). If well tolerated orally, alendronate and risedronate are preferable. Otherwise, zoledronate is preferred. Their efficacy vs. cost-safety-convenience ratio makes aminobisphosphonates reference drugs in the field of osteoporosis.

Multiple vertebral fractures after suspension of denosumab. A series of 56 cases.

BACKGROUND: Denosumab is a monoclonal antibody approved for the treatment of postmenopausal osteoporosis. The withdrawal of denosumab produces an abrupt loss of bone mineral density and may cause multiple vertebral fractures (MVF). OBJECTIVE: The objective of this study is to study the clinical, biochemical, and densitometric characteristics in a large series of postmenopausal women who suffered MVF after denosumab withdrawal. Likewise, we try to identify those factors related to the presence of a greater number of vertebral fractures (VF). PATIENTS AND METHODS: Fifty-six patients (54 women) who suffered MVF after receiving denosumab at least for three consecutive years and abruptly suspended it. A clinical examination was carried out. Biochemical bone remodelling markers (BBRM) and bone densitometry at the lumbar spine and proximal femur were measured. VF were diagnosed by magnetic resonance imaging MRI, X-ray, or both at dorsal and lumbar spine. RESULTS: Fifty-six patients presented a total of 192 VF. 41 patients (73.2%) had not previously suffered VF. After discontinuation of the drug, a statistically significant increase in the BBRM was observed. In the multivariate analysis, only the time that denosumab was previously received was associated with the presence of a greater number of VF (P = .04). CONCLUSIONS: We present the series with the largest number of patients collected to date. 56 patients accumulated 192 new VF. After the suspension of denosumab and the production of MVF, there was an increase in the serum values of the BBRM. The time of denosumab use was the only parameter associated with a greater number of fractures.

Calcifediol is superior to cholecalciferol in improving vitamin D status in postmenopausal women: a randomized trial.

Vitamin D has shown to play a role in multiple diseases due to its skeletal and extraskeletal actions. Furthermore, vitamin D deficiency has become a worldwide health issue. Few supplementation guidelines mention calcifediol treatment, despite being the direct precursor of calcitriol and the biomarker of vitamin D status. This 1-year, phase III-IV, double-blind, randomized, controlled, multicenter clinical trial assessed the efficacy and safety of calcifediol 0.266 mg soft capsules in vitamin D-deficient postmenopausal women, compared to cholecalciferol. Results reported here are from a prespecified interim analysis, for the evaluation of the study's primary endpoint: the percentage of patients with serum 25-hydroxyvitamin D (25(OH)D) levels above 30 ng/ml after 4 months. A total of 303 patients were enrolled, of whom 298 were included in the intention-to-treat (ITT) population. Patients with baseline levels of serum 25(OH)D <20 ng/ml were randomized 1:1:1 to calcifediol 0.266 mg/month for 12 months, calcifediol 0.266 mg/month for 4 months followed by placebo for 8 months, and cholecalciferol 25,000 IU/month for 12 months. At month 4, 35.0% of postmenopausal women treated with calcifediol and 8.2% of those treated with cholecalciferol reached serum 25(OH)D levels above 30 ng/ml (p < 0.0001). The most remarkable difference between both drugs in terms of mean change in serum 25(OH)D levels was observed after the first month of treatment (mean ± standard deviation change = 9.7 ± 6.7 and 5.1 ± 3.5 ng/ml in patients treated with calcifediol and cholecalciferol, respectively). No relevant treatment-related safety issues were reported in any of the groups studied. These results thus confirm that calcifediol is effective, faster, and more potent than cholecalciferol in raising serum 25(OH)D levels and is a valuable option for the treatment of vitamin D deficiency. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Lipid profile and serum folate, vitamin B12 and homocysteine levels in patients with retinal vein occlusion. / Perfil lipídico y concentraciones séricas de ácido fólico, vitamina B12 y homocisteína en pacientes con obstrucción venosa retiniana.

BACKGROUND: Retinal vein occlusion (RVO) is mainly related with vascular risk factors (VRF). OBJECTIVES: To analyze the lipid profile and serum folate, vitamin B12 and homocysteine levels, in patients with RVO and a population-based control group. PATIENTS AND METHODS: Case-control study. Patients with RVO were assessed during an 11-year period. RESULTS: We included 368 patients and 325 controls of similar age and sex. HDL cholesterol and folate levels were lower (52 [43-63] mg/dL vs. 55 [46-66]; p = 0.016 and 7 [5-10] ng/mL vs. 9 [7-13]; p < 0.0001, respectively) and non-HDL cholesterol and homocysteine levels higher (148.9 ± 37.3 mg/dL vs. 142.9 ± 34.5; p = 0.03 and 13.4 [11.2-18.2] µmol/L vs. 11.1 [9.0-14.4]; p < 0.001) in patients with RVO than controls. Although total cholesterol, LDL-C, and triglyceride levels were higher and serum vitamin B12 levels were lower in RVO patients, these differences did not reach statistical significance. CONCLUSIONS: RVO-patients have lower serum HDL-C and folate levels and higher non-HDL-C and serum homocysteine levels than population-based controls of similar age and sex. In patients with RVO, apart from the lipid profile, determination of serum homocysteine, folate and vitamin B12 levels might be useful, as well as the treatment of their alterations.

[Severe methotrexate toxicity in elderly: 7 years experience]. / Toxicidad grave por metotrexato en el anciano: nuestra experiencia en los últimos 7 años.

Methotrexate is one of the most widely used drugs in rheumatology due to its high efficacy-to-toxicity. However, patients treated with this drug are sometimes elderly, which increases toxicity risks, as well as mistakes in taking the medication. The case is presented of an 87 year-old patient, on multiple medications, with a history of cognitive impairment and low social support, who suffered acute methotrexate toxicity. A description is also presented on the characteristics of the toxicity cases due this drug admitted to this hospital in the last 7 years.

Interobserver agreement using Schlapbach graded scale for diffuse idiopathic skeletal hyperostosis (DISH): can we reduce the cut-off point of vertebral affection?

Resnick-Niwayama criteria for diagnosing DISH depict an advanced stage, and a new reduced cut-off point with three contiguous vertebrae affected (two bone bridges) has been proposed. The aim has been to know the interobserver agreement by using a graded scale of DISH in which grade II matches with the new proposed cut-off point and grade III matches with the first criterion of Resnick-Niwayama. Males ≥ 50 years and postmenopausal women included in a population-based prospective study (the Camargo Cohort) were analyzed. Sample size was obtained according to an expected kappa of 0.95 and an accuracy of ± 8%. Three physicians applied independently Schlapbach graded scale (ranged from grade 0, no ossification, to grade III, ≥ 3 consecutive bone bridges) on the lateral radiographs of thoracic and lumbar spine of participants. We calculated inter- and intra-observer agreement and correlation. One hundred and fifty eight radiographs (79 patients, 68 ± 9 years) were assessed. Kappa values (95% confidence interval) for grades 0, I, II, and III were 0.63 (0.50-0.77), 0.49 (0.37-0.62), 0.32 (0.17-0.47), and 0.69 (0.60-0.77), respectively. Weighted kappa for the three pairs of raters were 0.87 (0.82-0.93), 0.84 (0.77-0.91), and 0.81 (0.72-0.90). Grade III was the image that generated greater agreement, while a significant decrease was noted in grade II, the new proposed criterion. The simultaneous presence of an incomplete DISH and osteoarthritis, in a thoracic spinal segment with peculiar anatomical characteristics (reduced disk spaces, kyphotic curve), is thought to be a major cause of variability in the results.

Relationship between diffuse idiopathic skeletal hyperostosis, abdominal aortic calcification and associated metabolic disorders: Data from the Camargo Cohort. / Relación entre hiperostosis esquelética idiopática difusa, calcificación de la aorta abdominal y las alteraciones metabólicas asociadas: datos de la Cohorte Camargo.

BACKGROUND AND OBJECTIVE: Diffuse idiopathic skeletal hyperostosis (DISH) and abdominal aortic calcification (AAC) are related to an increased cardiovascular risk. The aim of this study was to analyse a possible relationship between both entities and also the association between metabolic disorders and DISH. PATIENTS AND METHOD: Analytic cross-sectional study in a population-based cohort. DISH (with Resnick-Niwayama criteria) and AAC (with AAC-24 scale) were assessed on plain x-ray images. Interaction terms between DISH and forty clinical covariates were also investigated, through correlation analysis and multivariate regression. RESULTS: Nine hundred eighty-seven males aged≥50 years, with a mean age=65,5±9 years, were evaluated. Prevalence rates of DISH and AAC were 21.6% and 58.7%, respectively. DISH+ subjects were older (68.1±9 vs. 63.8±9 years; P=.0001) and more likely to be affected by metabolic syndrome (MS) (55.6% vs. 36.6%; P=.0001). In DISH+ subjects, the AAC was 3.7±5 points, whereas in DISH- subjects it was 3.3±5 (P=.25). AAC was associated with an increased risk of prevalent DISH (unadjusted OR=1.4 [CI95%: 1.01-1.9]; P=.04), that disappeared when it was adjusted for age (adjusted OR=1.1 [CI95%: 0.8-1.5];P=.47]. No association was found between DISH and hypertension, diabetes or dyslipidaemia; however, age (OR=2.2 [CI95%: 1.6-3]; P=.0001), BMI (OR=1.5 [CI95%: 1.1-2]; P=.007), waist circumference (OR=1.5 [CI95%: 1.04-2,3]; P=.03) and MS (OR=1.7 [CI95%: 1.1-2.4]; P=.005) showed a significant relationship with DISH after adjusting for confounders. CONCLUSIONS: The study was not able to demonstrate a consistent association between DISH and AAC, proving only a weak and age-dependent relationship between them. DISH proved to be significantly associated with age, BMI, waist circumference and MS.

[Relationship between the plasmatic level of thyrotropin and cardiovascular disease (the Camargo Cohort)]. / Relación entre la concentración plasmática de tirotropina y enfermedad cardiovascular (Cohorte Camargo).

BACKGROUND AND OBJECTIVE: Age seems to modify the relationship between hypothyroidism and cardiovascular disease (CVD). Although hypothyroidism in very elderly subjects has been associated with longevity, subclinical hypothyroidism in people ≤ 65 years seems to be related with an increased cardiovascular risk (CVR). The aim of this study was to determine the explanatory power of plasmatic TSH (pTSH) for the CVD, in different strata determined by age (≤ 55, 56-74, ≥ 75 years), sex and CVR factors. PATIENTS AND METHODS: Six hundred and sixty-four men and women were differentiated into 18 strata and their explanatory models were developed using the multiple linear regression analysis. The dependent variable is the abdominal aortic calcification (AAC) according to the AAC-24 scale. The independent variables are: pTSH, age, smoking, BMI, SBP, DBP, fasting glucose, total cholesterol, HDL-cholesterol, LDL-cholesterol and C-reactive protein. RESULTS: Age is the main explanatory factor of AAC. The highest explanatory value of the ß-standardized coefficient of the pTSH is observed in males ≤ 55 years (ß=0.235, P=.043) and in females ≥ 75 years (ß=0.405, P=.042). With increasing age, the prediction power improves in women and decreases in men. In men ≥ 75 years there is a negative correlation between pTSH and AAC (rho-Spearman=-0.213, P=.049). CONCLUSIONS: A positive association is observed between pTSH and CVD in males ≤ 55 years and in women ≥ 75 years. The combination of multiple regression and the stratified analysis shows the complex influence of age in the relation between both variables.

Osteochemonecrosis of the jaws due to bisphosphonate treatments. Update.

Bisphosphonates (BP),were initially used in industry and later as a drug due to their great affinity to osseous tissue, because of their powerful antiresorptive effect as a treatment in various osteopathies, such as osteoporosis, Paget disease or hypercalcemia associated with some malignant tumors, as myeloma or breast cancer. They are administered orally or intravenously, and although well tolerated, the most frequent side effects are gastrointestinal, in addition to osteonecrosis when they are administered via endovenous. The aim of this work has been to evaluate the existing publications in accredited scientific literature on biphosphonates and their action mechanism and the relationship with the appearance of osteonecrosis of the jaws. Although the mechanism by which osteonecrosis of the jaws develops is not known exactly, there seems to be influence by osteoclast inhibiton, antiangiogenic action, an inhibitory effect on the cellular cycle by the keratinocytes, as well as, reinforcement of the chemiotoxic action in oncological patients treated with other drugs. Clinically, it ranges from a non-specificity of symptoms to lesions such as osteomyelitis with necrosis and osseous sequesters that may be accompanied by fetor ex oris, with the appearance of many Actinomyces contaminated lesions. As for published antecedents on osteonecrosis due to bisphosphonate treatment found until 2006: 46.5% had a previous diagnosis of multiple myeloma; 38.8% were patients with metastatic breast cancer; 6.2% patients of metastatic prostate cancer; 4.1% suffered from osteoporosis; 3.5% from other metastatic diseases and 0.8% had Paget disease. The drugs that seem to have the highest incidence of osteochemionecrosis are: zoledronate, pamidronate, alendronate, risendronate and ibandronate, from the greatest to the least. Additionally, the risk of osteonecrosis being produced is accumulative and may reach 21% in the third year of intravenous bisphosphonate use.

[Osteoporosis in cancer survivors]. / Osteoporosis tras la curación tumoral.

The detection of late sequelae in survivors of cancer has become increasingly important as developments in diagnostic and therapeutic methods have led to a more and long-term survival rates in tumoral patients. Osteoporosis is one of such problem that has been increasingly identified in patients with cancer. Significant bone loss and increased risk of fractures have been described in these patients. Medical problems associated with the malignancy or caused by the oncologic treatment are the main factors involved in bone loss. Therefore, patients at risk for bone loss should be undergo preventive or therapeutic interventions at an early enough stage to prevent fractures.