Prevalence of vitamin D deficiency and its prognostic impact on patients hospitalized with COVID-19.

OBJECTIVES: Although hypovitaminosis D appears to be highly prevalent in patients with coronavirus disease 2019 (COVID-19), its impact on their prognosis remains unclear. METHODS: In this study, serum 25-hydroxyvitamin D (Vit-D) level was measured in 200 patients hospitalized with COVID-19. The association between Vit-D and the composite endpoint of intensive care unit (ICU) admission/in-hospital death was explored using univariable and multivariable analyses. Also, serum Vit-D level in patients with COVID-19 was compared with that in age- and sex-balanced COVID-19-negative controls (i.e., 50 inpatients with sepsis). RESULTS: Serum Vit-D level was comparable between patients with COVID-19 and COVID-19-negative inpatients with sepsis (P = 0.397). No significant differences were found in serum Vit-D level according to COVID-19 severity at the time of hospital admission (P = 0.299). Incidence rates of the composite endpoint of ICU admission/in-hospital death did not differ significantly between patients with either Vit-D deficiency (i.e., Vit-D <20 ng/mL) or severe Vit-D deficiency (i.e., Vit-D <12 ng/mL) and those without (31% vs 35% with P = 0.649, and 34% vs 30% with P = 0.593, respectively). Vit-D level and status (i.e., Vit-D deficiency and severe Vit-D deficiency) were not prospectively associated with the risk of the composite endpoint of ICU admission/in-hospital death (P > 0.05 for all Cox regression models). CONCLUSIONS: Regardless of the potential usefulness of Vit-D measurement to guide appropriate supplementation, Vit-D does not appear to provide helpful information for the stratification of in-hospital prognosis in patients with COVID-19.

Association of parathyroid hormone and 25-OH-vitamin D levels with arterial stiffness in postmenopausal women with vitamin D insufficiency.

AIM: Vitamin D insufficiency and increased parathyroid hormone (PTH) levels have been suggested as prognostic indices for cardiovascular disease. Arterial stiffness, a surrogate marker for cardiovascular disease, is often increased in patients with primary hyperparathyroidism. PTH levels increase in patients with low 25-OH-vitamin D levels, but the influence of such an increase on arterial stiffness has not been investigated in postmenopausal women with reduced 25-OH-vitamin D levels. We therefore investigated the association between PTH and aortic stiffness in postmenopausal women with reduced 25-OH-vitamin D levels. METHODS: One hundred fifty postmenopausal women with 25-OH-vitamin D insufficiency (<30 ng/mL) were recruited. Aortic pulse wave velocity (aPWV), a measure of arterial stiffness, PTH and 25-OH-vitamin D levels were measured. Cardiovascular risk factors and markers of bone formation were evaluated. RESULTS: The 25-OH-vitamin D levels were associated with aPWV (rho=-0.23, p=0.006), but the association was not significant when controlling for PTH. Significant correlates of aPWV included age, body mass index, mean arterial pressure and PTH (rho=0.39, p<0.001). Arterial stiffness was predicted by logarithmically transformed PTH levels (ß=0.23, p=0.007), independent of traditional cardiovascular risk factors and factors involved in bone formation. Increased PTH levels (>62 pg/mL) were associated with a 3.0-5.4-fold increased probability of having a mild-severe increase in aortic stiffness, irrespective of confounders. CONCLUSION: Among postmenopausal women with reduced 25-OH-vitamin D levels, elevated PTH levels were a significant predictor of aortic stiffness, irrespective of cardiovascular risk factors and of factors involved in bone formation. PTH accounted for the association between 25-OH-vitamin D levels and aortic stiffness.

Transient osteoporosis of the hip: successful treatment with teriparatide.

A 62-year-old man presented with a 2-month history of increasing pain in the left hip. Magnetic resonance imaging (MRI) showed bone marrow edema (BME) of the left femur, dual energy X-ray absorptiometry (DXA) showed osteopenia at the same level, whereas pelvis X-rays failed to show any objective findings. After ruling out other possible causes of BME such as aseptic osteonecrosis, infectious arthritis, primary or metastatic malignancy, tuberculosis, osteomyelitis, rheumatoid arthritis, and seronegative spondyloarthropathies, a diagnosis of transient osteoporosis of the hip (TOH) was made, and treatment with teriparatide at a daily dose of 20 µg was started and continued for 4 weeks. Disappearance of the symptoms and normalization of MRI were obtained.

Osteoanabolic therapy: a non-surgical option of treatment for Kümmell's disease?

Kümmell's disease is the current eponym of avascular osteonecrosis (AVN) of a vertebral body leading to a delayed non-healing vertebral compression fracture (VCF) and thus pseudo-arthrosis. AVN is characterized by production of gas that outlines a radiolucent zone in the vertebral body, called vacuum cleft sign (VCS) or "Kümmell's sign". This sign has been observed in up to one-third of VCFs and is often associated with osteoporosis and never with malignant or inflammatory diseases. Generally, treatment strategies are conservative management and percutaneous vertebroplasty. Teriparatide (rhPTH [1-34]) is an osteoanabolic agent approved for treatment of osteoporosis and helpful in fracture's healing too. Here, we describe the case of an 81-year-old osteoporotic woman presented with a 1-year history of persistent low back pain onset after a trauma. A lumbar spine Computer Tomography (CT) scan performed 2 months after the injury (November 2006) showed the VCS within a VCF of the first lumbar vertebra; a control CT scan 1 year later showed persistence of the finding. After 12 months of treatment with teriparatide 20 mcg/day, symptoms disappeared and vacuum was significantly reduced. In conclusion, Kümmell's disease may be hypothesized in patients with chronic spinal symptoms, especially in the presence of osteoporosis. Moreover in this condition, osteoanabolic treatment may be used in patients with Kümmell's disease to enhance vertebral fracture's healing and contribute to back pain relief.

Association between thyroid hormone levels, the number of circulating osteoprogenitor cells, and bone mineral density in euthyroid postmenopausal women.

In postmenopausal women, an association between reduced bone mineral density (BMD) and increased number of circulating osteoprogenitor cells (COPs) has been found. Although an increased thyroid function is associated with BMD, thyroid hormones stimulate osteoblast function in vitro. We investigated whether thyroid hormones within the reference range were correlated with the number of COPs and stimulate mineralization in vitro. The number of COPs, defined as CD34+/alkaline phosphatase (AP)+ or CD34+/osteocalcin (OCN)+ cells, was quantified by fluorescence-activated cell sorting (FACS) analysis in 150 euthyroid postmenopausal women. Participants underwent measurement of serum free thyroxine (FT4), thyroid-stimulating hormone levels, and femur BMD. CD34+ cells were isolated from healthy volunteers irrespective of AP or OCN expression, and the effect of triiodothyronine (0.5-10 pmol/L)) on their ability to form mineralized nodules in vitro was studied. The number of COPs was highest among women with high-normal FT4 levels (>1.09 ng/dL). The FT4 levels were correlated positively with circulating log-CD34+/AP+ (r = 0.32, P < .001) and log-CD34/OCN+ cells (r = 0.36, P < .001) and inversely with total femur BMD (r = -0.17, P = .036) but not with femoral neck BMD. In a multivariate analysis, the FT4 levels were positively correlated with the number of COPs, independent of age and BMD. The ability of CD34+ cells to form mineralized nodules increased after exposure from low up to high-normal triiodothyronine concentrations (P for trend = .003). Among euthyroid postmenopausal women, high-normal FT4 levels are correlated with an increased number of circulating immature osteoprogenitor cells and a very mild BMD reduction. Exposure of CD34+ cells to physiological triiodothyronine concentrations stimulates mineralization in vitro.

Large-artery stiffness: a reversible marker of cardiovascular risk in primary hyperparathyroidism.

OBJECTIVE: Patients with primary hyperparathyroidism (pHPT) are at increased risk of cardiovascular mortality. We investigated whether aortic stiffness, an early marker of arteriosclerosis and a strong predictor of cardiovascular risk, is increased in pHPT, and whether it improves after parathyroidectomy. METHODS: Twenty-four patients with mild pHPT (age 56 ± 10 years, blood pressure 136/85 mmHg, serum calcium 2.55-3.00 mmol/L) and 48 control subjects individually matched with cases by age, sex and blood pressure underwent aortic (carotid-femoral) and upper-limb (carotid-radial) pulse wave velocity (PWV) determination by applanation tonometry in a case-control study. Subjects with renal disease, diabetes, treated hypertension or overt cardiovascular disease were excluded from the study. Seventeen of the patients with pHPT were re-examined 4 weeks after surgical parathyroidectomy. RESULTS: Aortic PWV was significantly higher among pHTP patients (11.4 ± 2 vs 9.6 ± 2 m/s, p<0.001). In a conditional logistic regression analysis, pHPT was independently associated with an increased risk of having an aortic PWV >12 m/s (odds ratio 3.28, 95% confidence interval 1.21-8.93). As expected, surgery was accompanied by a reduction in serum calcium (from 2.77 ± 0.2 to 2.25 ± 0.1 mmol/L, p<0.001) and parathyroid hormone (from 29.6 ± 10 to 3.3 ± 2 pmol/L, p<0.001). Aortic PWV decreased after surgery (from 10.9 ± 2 to 9.8 ± 2 m/s, p=0.003). The change in aortic PWV remained significant also after adjustment for changes in blood pressure (p<0.01). Changes in upper-limb PWV generally paralleled those in aortic PWV. CONCLUSION: pHPT is associated with increased aortic stiffness, which improves after parathyroidectomy. Our data demonstrate that aortic stiffness may improve upon removal of hyperparathyroid stimuli.

Carotid intima-media thickness and bone turnover: the role of C-terminal telopeptide of type I collagen.

Osteoporosis and vascular disease are commonly found together in elderly people. Several common mechanisms and risk factors have been suggested to contribute to the development of osteoporosis and atherosclerosis. The present cross-sectional study was performed to determine whether the degree of bone turnover is correlated to carotid intima-media thickness (CCA-IMT), as a marker of subclinical atherosclerosis. We selected 50 outpatients (mean age 71.7 +/- 12.3), underwent to eco-Doppler evaluation of extracranial carotid tract, without history of calcium and/or vitamin D supplementation, or antireabsorptive therapy. CCA-IMT was measured by high-resolution B-mode ultrasonography. Bone turnover was evaluated by analysing serum levels of C-terminal telopeptide of type I collagen (sCTX), and bone-specific alkaline phosphatase. We also evaluated the vitamin D status by determination of the serum concentration of 25-hydroxyvitamin D [25(OH)D]. We found a prevalence of hypovitaminosis D [serum 25(OH)D levels <30 ng/mL, mean value 10.7 +/- 5.8] of 91.8%, and an increased bone resorption, with mean sCTX levels higher than reference values (mean 1.18 +/- 0.57 ng/mL). A significant positive correlation was found between CCA-IMT and age (r = 0.480, P = 0.001), erythrocyte sedimentation rate (ESR: r = 0.438, P = 0.001), high-sensitivity C-Reactive Protein (HsCRP: r = 0.482, P = 0.011), serum creatinine (r = 0.305, P = 0.031), and sCTX (r = 0.389, P = 0.006). In a multivariate linear regression, CCA-IMT was independently predicted by age (beta = 0.34, P = 0.001), ESR (beta = 0.37, P = 0.005), and sCTX (beta = 0.32, P = 0.006). The preliminary results of our study seem to indicate that after adjustment for established cardiovascular risk factors, sCTX independently predict an increased CCA-IMT in the elderly population.

Diffuse muscoskeletal pain and proximal myopathy: do not forget hypovitaminosis D.

A 20-year-old vegetarian man was admitted to our hospital complaining of muscle weakness and gait disturbances of 4 years duration. For the past 5 years, he had major depression and had confined himself at home. He exhibited tenderness upon palpation of the chest, sternum and proximal muscles. Hypocalcemia, hypophosphatemia, vitamin D deficiency, increased levels of alkaline phosphatase, and intact parathyroid hormone were noted. An x-ray skeletal survey revealed generalized osteopenia, multiple vertebral and costal fractures, and a pelvis deformed into the shape of a triangle. A diagnosis of osteomalacia secondary to vitamin D deficiency from lack of exposure to sunlight and to inadequacy of the diet was made. The patient was started on a treatment with 20,000 IU of vitamin D3 once a week plus 1 g/d of calcium. Eight months later, gait disturbances have significantly improved and laboratory findings have all normalized.

High weight or body mass index increase the risk of vertebral fractures in postmenopausal osteoporotic women.

In the general population, low body weight and body mass index (BMI) are significant risk factors for any fracture, but the specific association between body weight, BMI, and prevalence of vertebral fractures in osteoporotic women is not fully recognized. Hence, the association between body weight, BMI, and prevalent vertebral fractures was investigated in 362 women with never-treated postmenopausal osteoporosis. All participants underwent measurement of BMI, bone mineral density (BMD), and semiquantitative assessment of vertebral fractures. Thirty percent of participants had > or =1 vertebral fracture. Body weight and BMI were associated with L1-L4 BMD (R = 0.29, P < 0.001 and R = 0.17, P = 0.009, respectively). In logistic regression analysis, BMI was positively associated with the presence of vertebral fractures independent of age and other traditional risk factors for fractures. Including weight and height instead of BMI in the multivariate model, showed weight as a positive and significant covariate of the presence of vertebral fractures (OR = 1.045; P = 0.016; 95% CI 1.008-1.084). BMI was associated with the number of vertebral fractures (rho = 0.18; P = 0.001), this association being confirmed also in the multivariate analysis (beta = 0.14; P = 0.03) after correction for smoking, early menopause, family history of fragility fractures and BMD. In conclusion, among postmenopausal women with osteoporosis, body weight and BMI are associated with a higher likelihood of having a vertebral fracture, irrespective of the positive association between weight and BMD.

Low bone mineral density in institutionalized patients with HIV and psychiatric co-morbidity.

Osteoporosis occurs in HIV-infected patients as well as in common psychiatric conditions and causes significant morbidity. There are no published studies assessing bone mineral density (BMD) in institutionalized HIV patients with associated psychiatric disorders. We analyzed 51 subjects in a case control study: 17 HIV patients (males or pre-menopausal females) with psychiatric co-morbidity and a long-term antipsychotic and antiretroviral therapy; and 34 control healthy subjects, not infected with HIV, matched with patients by age and sex. The results show that the HIV group had significantly higher rates of pathological T-scores, as compared with the controls (71% vs. 9% p<0.001). Chronic mental illness may represent a possible important co-factor influencing BMD in HIV patients. We suggest that fracture risk should be carefully evaluated for institutionalized HIV patients with psychiatric co-morbidity.

Cervical spondylodiscitis with spinal epidural abscess caused by Aggregatibacter aphrophilus.

Spondylodiscitis caused by Aggregatibacter aphrophilus, formerly known as Haemophilus paraphrophilus, is an unusual condition and can be very difficult to diagnose. We report a case of cervical spondylodiscitis complicated by spinal epidural abscess in a 63-year-old woman, without underlying predisposing conditions. The source of infection was identified as a periodontal infection. The patient was successfully treated with systemic antibiotics.

Loss of bone mineral density and secondary hyperparathyroidism are complications of autologous stem cell transplantation.

Patients who underwent autologous stem cell transplantation (ASCT) are prone to decreased bone mineral density (BMD). We measured BMD in 180 patients who underwent ASCT for hematologic malignancies. Patients were evaluated with a median of 6.2 years after ASCT. Twenty patients who received only chemotherapy were evaluated as controls. The loss of bone mass was greater during the first year after ASCT, since majority of patients recover BMD and normalize bone turnover markers during the following years. After ASCT, over half of the patients show osteopenia or osteoporosis independent of the sex. According to the results of other groups, our results emphasize the potential usefulness of antiresorptive agents to prevent or treat post-ASCT osteopenia or osteoporosis, and the importance of the measurement of BMD as an integral component to the follow-up of ASCT.

Simvastatin increases bone mineral density in hypercholesterolemic postmenopausal women.

Statins are able to reduce cardiovascular morbility and mortality mainly through their hypocholesterolemic effect. Beyond the inhibition of cholesterol synthesis, the identification of "ancillary" mechanisms has motivated studies evaluating the relationship between the use of statins and the modification of bone mineral density (BMD). To date, clinical trials have provided discordant results. The aim of our study was to evaluate whether simvastatin treatment (40 mg/d) could modify BMD in hypercholesterolemic women (n = 40) after a 2-year treatment as compared with a control group treated only with diet (n = 20) and matched by gender, age, body mass index (BMI), lipids, menopausal age, and BMD and the number of osteopenic, osteoporotic, and normal women (on the basis of T-score value). Exclusion criteria were secondary hyperlipemias and osteoporosis and current or previous therapy with statins, bisphosphonates, and estrogens. The BMD was measured at the lumbar spine and hip by dual energy x-ray absorpiometry (DEXA). In the group treated by simvastatin, BMD, both on the spine and femoral hip, showed a significant increase after 8 and 24 months, respectively (0.878 +/- 0.133 v 0.893 +/- 0.130 and 0.907 +/- 0.132; 0.840 +/- 0.101 v 0.854 +/- 0.101; and 0.863 +/- 0.10, P <.001); there was a percentage increase of 1.7% after 8 months and 3.3% after 24 months at the spine; at the femoral hip, BMD increased 1.6% after 8 months and 2.7% after 24 months. The group treated only with hypolipidic diet demonstrated after 8 and 24 months a slight decrease in BMD both on the spine and femoral hip (respectively, 0.884 +/- 0.175 v 0.872 +/- 0.174 and 0.861 +/- 0.164; 0.860 +/- 0.110 v 0.853 +/- 0.096 and 0.847 +/- 0.095; P <.05). In conclusion, as partly suggested by retrospective or observational data, this longitudinal study indicates that simvastatin treatment exerts a beneficial effect on BMD.