2019 Qeios
Projects

Definition:

Bisphosphonate related osteonecrosis of the jaw (BRONJ)

My review

MRONJ follows nitrogen-containing bisphosphonates (NCB).

Metabolic effects of NCB :

Effect of NBPs on Mevalonate Pathway (http://flipper.diff.org/app/items/info/388)

The inhibition of farnesyl diphosphate synthase (FPP) leads to

an increase of uphill substrates (IPP)
a decrease of downhill substrates (cholesterol, CoQ10, farnesylPP and related metabolisms)

The decrease of CoQ10 slows the respiratory chain rate, reducing the intracellular ATP.
Results: Cases and controls did not differ for any study variable except for vascular congestion that was significantly associated with NBP use (multivariable OR = 0.24, exact 95% CI 0.10 to 0.57 for cases vs. controls, p = 0.0006).

NOS /ATP

NBP

heme synthesis http://flipper.diff.org/app/pathways/info/81

https://www.ncbi.nlm.nih.gov/pubmed/30675875
Epidermal Growth Factor Reverses the Inhibitory Effects of the Bisphosphonate, Zoledronic Acid, on Human Oral Keratinocytes and Human Vascular Endothelial Cells In Vitro via the Epidermal Growth Factor Receptor (EGFR)/Akt/Phosphoinositide 3-Kinase (PI3K) Signaling Pathway. 2019

Zoledronic acid treatment of HOKs and HUVECs had no significant effects on apoptosis (P>0.05), but significantly reduced expression levels of p-EGFR, p-Akt, p-PI3K, p-mTOR), and p-eNOS (P<0.05); EGF partially reversed these effects and increased the expression levels (P<0.05). CONCLUSIONS EGF partially reversed the effects of the bisphosphonate, zoledronic acid, on HOKs and HUVECs in vitro via the EGFR/Akt/PI3K signaling pathway. Further studies are required to determine the effects of EGF on MRONJ including bisphosphonate-related osteonecrosis of the jaw.

osteosclerosis

https://doi.org/10.1111/j.1601-0825.2012.01903.x

MANAGEMENT OF ENDOCRINE DISEASE: l-Thyroxine replacement therapy in the frail elderly: a challenge in clinical practice. (2017) https://doi.org/10.1530/EJE-17-0321
The prevalence of overt and subclinical hypothyroidism is as high as 20% and thyroid hormone prescription is common in the elderly, with a trend toward levothyroxine treatment of more marginal degrees of hypothyroidism.

Dr David Brownstein salt in diet