Teriparatide (recombinant human parathyroid hormone [1‐34]) increases foot bone remodeling in diabetic chronic Charcot neuroarthropathy: a randomized double‐blind placebo‐controlled study

Abstract

Highlights• Charcot neuroarthropathy (CN) is associated with demineralization of foot bone, but there is no established medical treatment for chronic CN.• This study explored the role of teriparatide in chronic CN and demonstrated a significant increase in foot bone remodeling with teriparatide. AbstractBackground: Currently, there is no consensus regarding the medical treatment of chronic Charcot neuroarthropathy (CN) of foot, except for effective off-loading. Because tarsal bones are predominantly trabecular, teriparatide may improve the macroarchitecture of foot bones in chronic CN. Methods: People with diabetes and chronic CN were randomized to receive either 20 μg teriparatide or placebo subcutaneous daily for 12 months. Thirty-eight patients were screened and data were analyzed for 20. The maximum standardized uptake (SUV max ) value of 18 F-FDG PET/CT the region of interest, bone turnover markers and foot bone mineral density BMD were determined. The primary outcome measure was change in SUV max g/ml. Results: Mid-foot was the most common region involved. After 12 months, SUV max increased from 30.6 ± 14.7 to 37.7 ± 18.0 (P = 0.044) in the teriparatide group, but decreased from 27.6 ± 12.2 to 22.9 ± 10.4 with placebo (P = 0.148). The estimated treatment difference (ETD) was 11.9 ± 4.3 (95% CI 2.9, 20.8; P = 0.012). Similarly, P1NP increased with teriparatide (19.8 ± 5.5; P = 0.006) but decreased with placebo (−5.1 ± 3.8 ng/mL; P = 0.219); ETD was 24.8 ± 6.6 (95% CI 10.8, 38.8; P < 0.001) and CTX increased in both the teriparatide and placebo groups. Foot BMD increased by 0.06 ± 0.04 g/cm 2 (P = 0.192) with teriparatide, but decreased by −0.06 ± 0.08 g/cm 2 with placebo (P = 0.488; intergroup comparison, P = 0.096).

BMP9 Reduces Bone Loss in Ovariectomized Mice by Dual Regulation of Bone Remodeling

“…Pharmacological agents for the treatment of osteoporosis can be classified as either antiresorptive or anabolic . However, because of the coupling and synchronization of bone resorption and new bone formation, anti‐bone resorption drugs can inhibit both bone resorption and bone formation, while anabolic drugs, such as parathyroid hormone (PTH) or parathyroid hormone–related protein (PTHrP), mainly enhance bone formation and meanwhile stimulate bone resorption . Researchers are constantly striving to explore dual‐action agents that modulate bone remodeling for the treatment of osteoporosis, such as an anti‐sclerostin antibody that is now available on the market and several others that are under investigation …”

Differential Abatement of Inflammation And Osteoclastogenesis In Active Charcot Neuroarthropathy: Mechanistic Insights From Randomized Controlled Study

“…[15] However, whether the initial gain in BMD persists after the quiescence of clinical activity needs to be assessed in long term follow-up studies. Though teriparatide has been shown to increase foot bone BMD in patients of chronic CN of foot, [22] its e cacy needs to be evaluated in patients of active CN.…”

“…ROI was drawn manually and BMC quanti ed. [22] Blood sample for biochemistry, bone turnover markers (BTMs) and in ammatory cytokines were collected after an overnight fast (8-10 hours) at 0800-0900h from the antecubital vein. BTMs, namely procollagen I intact N-terminal (P1NP) and carboxy terminal collagen crosslink (CTX) peptides were estimated by electrochemiluminiscence assay (ECLIA) (Roche COBAS600, Germany) with an inter-assay coe cient of variation (CV) of 1.7 to 3.2%, intra-assay CV of 4.1% for P1NP and inter-assay CV of 1.2 to 4.7%, intraassay CV of 1.9% for CTX.…”

SIRT2 deficiency prevents age-related bone loss in rats by inhibiting osteoclastogenesis

“…A: Tb. BMD (g/cm 3 ), trabecular bone mineral density; B: BV/TV (%), bone volume per total volume; C: BS/TV (mm -1 ), bone surface per total volume; D: Tb. N (mm -1 ), trabecular number; E: Tb.…”

“…Bone remodeling is regulated by matrix-forming osteoblasts and bone-resorbing osteoclasts under the coordination of various elements such as cytokines, growth factors, adaptor proteins and hormones (1)(2)(3)(4). Osteoclasts are giant multi-nucleated cells that differentiate from hematopoietic cell lineages of monocyte/ macrophages (5).…”