pyrophosphate and Osteoporotic-Fractures

Despite their proven efficacy for secondary fracture prevention, long-term adherence with oral bisphosphonates is poor.. To compare the effectiveness of two interventions on long-term oral bisphosphonate adherence after an upper extremity fragility fracture.. Community-dwelling participants 50 years or older with upper extremity fragility fractures not previously treated with bisphosphonates were randomized to either a multi-faceted patient and physician educational intervention (the active control arm) vs. a nurse-led case manager (the study arm). Primary outcome was adherence (taking > 80% of prescribed doses) with prescribed oral bisphosphonates at 12 months postfracture between groups; secondary outcomes included rates of primary non-adherence and 24-month adherence. We also compared quality of life between adherent and non-adherent patients.. By 12 months, adherence with the initially prescribed bisphosphonate was similar (p = 0.96) in both groups: 38/48 (79.2%) in the educational intervention group vs. 66/83 (79.5%) in the case manager arm. By 24 months, adherence rates were 67% (32/48) in the educational intervention group vs. 53% (43/81) in case managed patients (p = 0.13). Primary non-adherence was 6% (11 patients) in the educational intervention group and 12% (21 patients) in the case managed group (p = 0.07). Prior family history of osteoporosis (aOR 2.1, 95% CI 1.0 to 4.4) and being satisfied with current medical care (aOR 2.3, 95% CI 1.1 to 4.8) were associated with better adherence while lower income (aOR 0.2, 95% CI 0.1 to 0.6, for patients with income < $30,000 per annum) was associated with poorer rates of adherence. There were no differences in health-related quality of life scores at baseline or during follow-up between patients who were adherent and those who were not.. While both interventions achieved higher oral bisphosphonate adherence compared to previously reported adherence rates in the general population, primary non-adherence and long-term adherence to bisphosphonates were similar in both arms. Adherence was influenced by family history of osteoporosis, satisfaction with current medical care, and income.. ClinicalTrials.gov : NCT01401556.

Topics: Administration, Oral; Aged; Alberta; Bone Density Conservation Agents; Case Management; Diphosphates; Female; Humans; Male; Medication Adherence; Middle Aged; Osteoporosis; Osteoporotic Fractures; Patient Education as Topic; Psychometrics; Quality of Life; Recurrence; Secondary Prevention; Socioeconomic Factors; Upper Extremity

Tissue non-specific alkaline phosphatase (TNSALP) is an enzyme that is tethered to the cell membrane by glycosylphosphatidylinositol (GPI) and converts inorganic pyrophosphate to inorganic phosphate. Inorganic phosphate combines with calcium to form hydroxyapatite, the main mineral in the skeleton. When TNSALP is defective, conversion of inorganic pyrophosphate to inorganic phosphate is impaired and the skeleton is at risk of under-mineralization. Phosphatidylinositol glycan anchor biosynthesis class N (PIGN) is one of more than 20 genes in the GPI-biosynthesis family. Pathogenic variants in PIGN have been identified in multiple congenital anomalies-hypotonia-seizures syndrome (OMIM 614080), although a metabolic bone disease or skeletal fragility phenotype has not been reported. We describe a female child with multiple congenital anomalies-hypotonia-seizures syndrome due to a compound heterozygous pathogenic variant in PIGN who sustained a low-trauma distal femur fracture at age 7.4 years. We hypothesized that the GPI synthesis defect may result in metabolic bone disease from inadequate anchoring of TNSALP in bone and initiated asfotase alfa, a human bone-targeted recombinant TNSALP-Fc-deca-aspartate peptide, as it could bypass the PIGN genetic defect that possibly caused her skeletal fragility. Asfotase alfa was begun at 8.5 years. Baseline X-rays revealed mild rachitic findings of wrists and knees, which resolved by 5 months of treatment. Bone mineral density (BMD) assessed by dual-energy X-ray absorptiometry (DXA) showed mild improvement in spine, hip and total body less head after 16 months of treatment, while radius declined. She sustained additional low trauma fractures at right tibia and left humeral neck at 11 and 15 months into treatment, which healed quickly. Calcium, phosphorus, and parathyroid hormone levels have remained within the normal range over the 18 months of treatment. For adverse effect, she experienced a rash and discomfort in the first week of treatment which resolved with ibuprofen and diphenhydramine. She also developed subcutaneous fat atrophy. Overall, in this child with a compound pathogenic variant in PIGN, off-label use of asfotase alfa has been generally well tolerated with minimal side effects and resolution of rickets, but she continues to remain skeletally fragile.

Topics: Alkaline Phosphatase; Bone and Bones; Bone Diseases, Metabolic; Calcinosis; Calcium; Calcium, Dietary; Child; Diphosphates; Female; Fracture Healing; Humans; Hypophosphatasia; Muscle Hypotonia; Osteoporotic Fractures; Seizures