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.

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.

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.

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.

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.