Bone Abstracts

ExFOS is a multicenter, prospective, observational study to evaluate fracture outcomes, back pain, compliance and health-related quality of life in female and male patients with osteoporosis treated with teriparatide [rhPTH(1–34)] (Forsteo)for 18 to 24 months. Post-treatment follow-up will last for at least 18 months. Patients were enrolled in Croatia, Denmark, France, Greece, Italy, Norway, Slovenia, and Sweden. The study design was non-interventional and all consenting ...

Objectives: Hypophosphatasia (HPP) is a rare metabolic disease caused by loss-of-function mutation(s) in the tissue-nonspecific alkaline phosphatase (TNSALP) gene. Resultant low TNSALP leads to defective skeletal mineralization and diverse complications that may include poor growth, proximal muscle weakness, pain, and compromised physical function in children. Here, we describe the burden of HPP in patients <18 years old as assessed by two surveys specific to HPP symptomol...

Objectives: Hypophosphatasia (HPP) is a rare metabolic disease caused by loss-of-function mutation(s) in the gene encoding tissue-nonspecific alkaline phosphatase (TNSALP). HPP in infants is characterized by poor skeletal mineralization, respiratory compromise, and a high risk of mortality. We previously reported improved mineralization and respiratory function in 15 patients enrolled in this second study of asfotase alfa, a bone-targeted recombinant human TNSALP, in infants a...

Osteoporosis is generally accompanied by the fatty degeneration of the bone marrow. The enhanced deposition of adipocytes may result from adipogenic differentiation of bone-marrow mesenchymal stem cells (MSC) and from the adipogenic conversion of osteoblastic cells respectively. Thus, whether this clinical observation is a cause of the disease or rather a reaction of the afflicted bone marrow remains to be elucidated.Previous microarray and bioinformatic...

Background: Hypophosphatasia (HPP) results from inactivating mutation(s) in the gene for tissue non-specific alkaline phosphatase (TNSALP). Substantial improvement has been reported in skeletal mineralization and physical function in patients (pts) with life-threatening perinatal and infantile HPP treated for 48 weaks with asfotase alfa, a bone-targeted recombinant human TNSALP.Objective: To evaluate long-term efficacy and tolerability of asfotase alfa i...

Reduced peripheral serotonin (5HT) in mice lacking tryptophan hydroxylase (TPH1), the rate limiting enzyme for 5HT synthesis, was reported to be anabolic to the skeleton. However, in other studies, TPH1 deletion either had no bone effect or an age-dependent inhibition of osteoclastic bone resorption. The role of 5HT in bone therefore remains poorly understood. To address this issue, we used selective breeding to create rat sublines with constitutively high (high-5HT) and low (...

Although bone morphogenetic protein 6 (BMP6) is known for its ability to induce growth of bone and cartilage, recent studies identified BMP6 as a key endogenous regulator of hepcidin expression and iron metabolism. Here, we examined BMP6 presence in the serum and investigated whether circulating levels of BMP6 may reflect body iron status. First, we showed by liquid chromatography–mass spectrometry (LC–MS) and western blotting that BMP6 is present in the circulation ...

Background: Hypophosphatasia (HPP) is caused by inactivating mutation(s) in the gene for tissue non-specific alkaline phosphatase. Extracellular accumulation of inorganic pyrophosphate can lead to profound hypomineralization resulting in limb and chest deformity, respiratory complications and vitamin B6-dependent seizures in the severe forms of HPP. The natural history of HPP is poorly understood, but the perinatal and infantile forms are often considered lethal.<p class="...

Objectives: Pediatric vitamin D (25-hydroxyvitamin D - 25OHD) deficiency can lead to nutritional rickets and extra-skeletal complications. Compliance with daily therapy can be difficult, making high dose, short-term vitamin D (stoss) therapy attractive to correct vitamin D deficiency. We compared the effectiveness and safety of standard versus stoss therapy in treating childhood 25OHD deficiency.Study design: Children aged 2–16 years with 25OHD &#60...

Elevated levels of circulating serotonin have been reported to decrease bone mineral density1. Conversely, reduced serotonin (5HT) in mice lacking TPH1, the rate limiting enzyme for 5HT synthesis, was reported to be anabolic to the skeleton with high osteoblastic activity2. However, in other studies TPH1 deletion led to either an initial increase in BMD due to inhibition of osteoclastic bone resorption3, or had no bone effect4</su...