Table 2.

Mechanisms of bone degeneration and loss under various disease conditions

Disease	Mechanisms of bone degeneration and loss	Key references
Type II Diabetes	Increased inflammation	Shen et al.[ 26 ]
	Increased ROS production/oxidative stress	Tang et al.[ 27 ]
	Accumulation of advanced glycation end products (AGEs)	Yamamoto & Sugimoto[ 28 ] Karim & Bouxsein[ 29 ]
	Inhibition of angiogenesis	Lim et al.[ 30 ] Caliaperoumal et al.[ 31 ]
	Impairment of osteoblast function	Peng et al.[ 32 ] Wongdee et al.[ 33 ] Park et al.[ 34 ] Lee et al.[ 35 ]
Osteoporosis	Age‐related decline in hormonal/estrogen levels	Cheng et al.[ 39 ] Gosset et al.[ 40 ] Emmanuelle et al.[ 41 ] Bjørnerem et al.[ 42 ]
	Age‐related decline in proliferative capacity, plasticity and number of endogenous mesenchymal stem cells	Li et al.[ 43 ] Li et al.[ 44 ]
	Vitamin D deficiency in older patients	Al‐Daghri et al.[ 45 ] Föger‐Samwald et al.[ 46 ]
Periodontitis	Inflammation triggered by bacterial infection/LPS on bacterial cell membrane	Page et al.[ 50 ]
	Inflammatory cascade promotes osteoclastogenesis/bone resorption	Zhou et al.[ 53 ] Yang et al.[ 54 ] Choi et al.[ 55 ]
	Inflammatory cascade suppresses osteoblast differentiation and function	Kaneshiro et al.[ 56 ] Zou & Bar‐Shavit[ 57 ]
Osteoarthritis	Exposure of sub‐chondral bone to pro‐inflammatory cytokines secreted by OA chondrocytes	Chien et al.[ 75 ]
	Pro‐inflammatory cytokines promote osteoclastogenesis and bone resorption	Lee et al.[ 76 ] Yang et al.[ 77 ] Lam et al.[ 78 ] Marahleh et al.[ 79 ] Kudo et al.[ 80 ]
Rheumatoid arthritis	Inflammatory cascade promotes osteoclastogenesis and bone resorption	Goldring[ 81 ]
	Reduced bone mineralization due to deficiency of vitamin D, calcium and other mineral absorption	Bellan et al.[ 82 ]
Osteomyelosis	Bacterial infection causes apoptosis of osteoblasts, which promotes osteoclastogenesis	Claro et al.[ 86 ]
	Staphylococcal Protein A (SpA) secreted by S. aureus promotes osteoclastogenesis	Widaa et al.[ 87 ] Chen et al.[ 88 ] Mendoza Bertelli et al.[ 89 ]
	Inflammatory cascade activated by bacterial infection promote osteoclastogenesis and bone resorption	Lan et al.[ 92 ]
	Demineralization caused by increased expression of matrix metalloproteinase (perilacunar remodeling/osteocytic osteolysis)	Ormsby et al.[ 93 ] Gunn et al.[ 94 ]
Metastatic osteolysis	Metastatic cells secrete growth factors and cytokines that promote osteoclastogenesis and bone resorption	Giannoni et al.[ 99 ] Sethi et al.[ 100 ] Lu et al.[ 101 ] Andrade et al.[ 102 ]
	Altered metabolism and bioenergetics by metastatic cancer cells promote osteoclastogenesis and bone resorption	Tiedemann et al.[ 104 ]
	Metastatic cancer cells induce hypoxia and trigger HIF signaling that suppress osteoblastic differentiation and promote osteoclastogenesis	Xu et al.[ 105 ] Todd and Johnson[ 106 ]