Teriparatide is safe and effectively increases bone biomarkers in institutionalized individuals with osteoporosis

Abstract

Institutionalized adults with severe developmental disabilities have a high rate of minimal trauma and appendicular fracture. There is little information about osteoporosis treatment in this population. In this efficacy and safety study, men and women with severe developmental disabilities and osteoporosis received 20 mcg teriparatide subcutaneously daily for 18-24 months. Markers of bone formation [procollagen type 1 intact N-terminal propeptide (P1NP)] and resorption [C-telopeptide (CTx)] were measured at three-month intervals. Serum calcium was measured at two-week intervals for 12 weeks and thereafter at three-month intervals. Twenty-seven individuals received at least one injection. The incidence of hypercalcemia was 11.1% but was persistent and led to medication discontinuation in only one participant. Biomarkers of bone formation increased rapidly, doubling by three months. At 12 months, P1NP and CTx remained elevated from baseline; P1NP had risen from 66.95 +/- 83.71 microg/l (mean +/- SD) to 142.42 +/- 113.85 microg/l (P = 0.05), and CTx had increased from 0.377 +/- 0.253 to 1.016 +/- 1.048 ng/ml (P = 0.01). The majority of participants had an increase in P1NP of over 10 microg/l. In conclusion, teriparatide is safe and effective in developmentally disabled institutionalized adults. Serial calcium measurements are warranted, particularly during the first three months of therapy.

Tissue engineered bone using select growth factors: A comprehensive review of animal studies and clinical translation studies in man

“…Horwitz et al (2011) indeed demonstrated extensive bone resorption with high dose PTH (4 pmol/kg/h) delivered by continuous infusion pump, resulting in hypercalcemia. Intermittent delivery increased bone turnover within low BMD patients who exhibited 2.1 fold increased bone formation, and 2.7 fold increased bone resorption (Ryder et al, 2010). Nakamura et al (2012) also demonstrated increased BMD (2.3 to 6 fold) within vertebral fracture patients following intermittent administration (56.5 μg/week).…”

“…PTH has been administered in humans for many years investigating its efficacy for bone formation within healthy adults (Horwitz et al, 2011), adults with low BMD (Ryder et al, 2010), postmenopausal women (Schafer et al, 2013), mandibular defects (Kwon et al, 2012) and vertebral fractures (Supplementary Table 5). Continuous delivery has been shown to reduce bone formation markers and increase bone resorption.…”

Biochemical markers of bone turnover – uses and limitations

“…Its synthesis is stimulated by 1,25-dihydroxyvitamin D. OC contains three glutamic acid residues, which are converted to gamma-carboxyglutamate (gla) by vitamin K-dependent post-translational carboxylation. 2,17 The carboxylation process leads to a conformational change in protein which allows the binding of OC with hydroxyapatite and mineralization in the bone matrix. There are also non-carboxylated or undercarboxylated forms of OC released into the circulation, 24 but its significance in postmenopausal osteoporosis fracture prediction is less than intact OC.…”

“…16 Procollagen peptide concentrations are reduced by antiresorptive treatments (such as oestrogen and bisphosphonates) and are increased by the anabolic agents such as teriparatide (human recombinant parathyroid hormone). 17,18 Bone-specific alkaline phosphatase. Alkaline phosphatase (ALP) is a membrane-bound enzyme and is present in almost all body tissues.…”

Probable osteosarcoma risk after prolonged teriparatide treatment: Comment on the article by Saag et al

“…Its use has been approved by the US Food and Drug Administration (FDA) only for adults (1). Contraindications to the use of teriparatide include the following: any hypercalcemic disorder, osteosarcoma, metastatic bone disease, Paget's disease of bone, pregnancy, and radiation therapy to the skeleton or to soft tissue in which a skeletal port is exposed.…”