Bone health and the role of nutrients and diets during ageing
(Describe and discuss the role of nutrients and dietary components in the support of healthy bones during ageing)
Bone modelling and re-modelling:
Four types of bone cells in bone tissue:
Osteogenic cells: undifferentiated cells that develop into soteoblasts
When osteoblasts (maintains bone tissue) get trapped within the calcified matrix, their structure and function changes and they become osteocytes (stem cell)
Osteoclast (resorbs bone): develop from monocytes and macrophages and differ in appearance from other bone cells
Osteoblasts:
Single nucleated cells
(a) synthesise bone cells and in this process, they function in groups of connected cells. individual cells cannot make bone
(b) secrete a variety of proteins and extracellular matrix materials that make up bone tissue
(c) regulate the mineralisation of the bone tissue by producing and depositing calcium and phosphate ions
Osteoclasts:
Large, multinucleate cells
(a) responsible for breaking down and resorbing bone tissue
(b) are unique in their ability to dissolve the mineralise matrix of bone tissue by secreting enzymes and acids that break down the organic and inorganic components of bone tissue, releasing calcium nd phosphate ions into the bloodstream
Cortical bones: a relatively slower turnover rate because of higher density
Trabecular bone: a relatively higher turnover rate (a higher proportion of surface area to volume)
Bone remodelling:
Old, brittle bone tissue is removed or resorbed and replaced by new tissue
--> reshaping bones after a fracture
--> repairing micro-cracks (form when bones are under stress)
Surface of bone is covered by periosteum consisting of:
(a) outer fibrous layer - protects bones and provides attachment for tendons and ligaments
(b) inner cellular layer - progenitor stem cells --> forms osteoblasts and chondroblasts (produce cartilage)
Spongy bone: cross-linking roads called trabeculae --> resistant to mechanical stress
The spaces in the spongy bone is occupied by bone marrow
Bone marrow:
Hematopoietic stem cells (blood-making cells) --> lymphoid progenitor cells --> B and T-cells, myeloid progenitor cells (RBC, platelets, myeloblasts)
Bone remodelling process:
Osteoblasts sensed micro-cracks in a specific location and produces RankL (receptor activation of nuclear factor kbeta ligand)
RankL induces monocytes to fuse together to form a multinucleate osteoclast cell and it also helps the osteoclast mature and activate so that they can start resorbing
Osteoclast starts secreting lysosomal enzymes (collagenase) --> digest collagen protein in the organic matrix
Osteoclasts also produce HCl which dissolved hydroxyapatite into soluble calcium and phosphate ions, which are released into bloodstream.
There are scattering of osteocytes which are trapped within the bony matrix --> when freed up by the dissolving of bone, they get phagocytosed by the osteoclasts.
Osteoblasts also release osteoprotegerin which binds to RankL to slow down activation of osteoclasts.
Osteoblasts secrete osteoid seam to fill in lacunae within bony matrix turning into osteocytes
Bone remodelling is affect by various hormones:
Parathyroid glands release PTH in reasons not decrease in blood calcium resulting in release of RankL, leading to bone resorption (to increase blood calcium)
Parafollicular cells produce calcitonin, a higher calcitonin inhibits bone resorption and reduces blood calcium
Bone remodelling is also affect by mechanical stress:
- Bones that bear a lot of weight remodel at a high rate (Wolff's law)
Vitamin D:
- Stimulate intestinal absorption of calcium --> increases calcitonin levels and inhibits bone resorptio
Bone disorders related to bone and ageing
Osteomalacia
Disorder of “bone softening” in adults that is usually due to prolonged deficiency of vitamin D.
Causes: Vitamin D deficiency
Symptoms: pain felt in the bones and joints, muscle pain and weakness, particularly following exercise
Treatment: high dose of vitamin D (800 to 4,000IU)
Osteoporosis:
Symptoms: severe back pain, loss of height, or spine malformations such as a stooped or hunched posture
Causes: decrease in bone density, ageing, long-term lack of calcium
Treatment: calcium and vitamin D supplementation, low-impact physical activity
Diagnosis:
Reference measurement is derived from bone density measurements in a population of healthy young adults (called T-score)
Osteoporosis --> T-score of -2.5 or lower
Other nutrients and bioactive factors that influence bone health
Nutrients in relation to bone mass: calcium and vitamin D
Calcium absorption with ageing:
- calcium absorption: active and passive
- calcium absorption decreases with age due to
(i) reduction in serum 25(OH)D concentration
(ii) impaired hydroxylation of 25(OH)D to 1,25(OH)2D
(iii) resistance to the action of vitamin D metabolites on the bowel mucosa
(iV) in women: low circulating oestrogen concentrations
65% of the total calcium absorption takes place in the ileum (3rd section of the small intestine)
Vitamin D metabolism and ageing:
Sunlight converts 7-dehydrocolesterol stored in our skin to 25(OH)D in the liver.
Our kidneys convert 25(OH)D to 1,25(OH)2D, which is the active metbaolite
This is dependent on blood calcium concentration and PTH (lower calcium = higher PTH)
Role of vitamin D in regulation of calcium homeostasis:
(1) Low blood calcium signals parathyroid glands to release PTH
(2) This stimulate kidneys to increase ca2+ resorption and increases blood calcium levels
(3) This then stimulates renal-hydroxylate to convert 25(OH)D3 to 1,25(OH)2D3
(4) The increased blood calcitriol and stimulates Ca2+ absorption in intestine
(5) Increased PTH and calcitriol stimulate resorption of Ca2+ and phosphate from bone
Determinants of peak bone mass (PBM):
Genetic influence:
(a) 70-80% of the variation in bone mass ia due to genes
(b) the remaining variation may be explained by lifestyle factors such as nutrition, physical activity and smoking
Saturated fatty acids (SFAs)
Palmitic acid (16-C SFA) is one of the most common SFAs found in the human body and diet. It is reported to induce the apoptosis of osteoblasts and enhance survival of osteoclasts.
Mechanisms: close relationship between bone and lipid metabolism, esp. in human bone marrow
Mechanism:
Palmitate is a ligand of toll-like receptors 2 (TLR2) and TLR4 in the human monocytes, which subsequently activates mitogen-activated protein kinases (MAPK) and nuclear factor kB (NF-kB) signalling pathways.
Unsaturated fatty acids
Omega 6
Effects: omega-6 FAs shown to decrease hip and trochanter BMDin postmenopausal women --> increase risk of osteoporosis; omega-6 FAs shown to decrease total fracture risk, hip fracture
risk, and increase the total body BMD
Mechanisms: Decreasing calcium absorption (due to the formation of calcium-fatty acid soaps), and inducing the release of inflammatory cytokines
Omega 3
Effects: could inhibit osteoclast differentiation and formation, enhance osteoblast activity, inhibit formation of osteoclasts, and facilitate calcium transport in the gut
Mechanisms: Activating receptors expressed in osteoblasts, osteoclasts. Possibly also positively affecting the structures of lipid membranes, which paly roles in the passibe uptake of calcium
Mechanisms of bioactive peptides:
Caseinphosphopeptides
(CPPs) --> preventing Ca precipitation in intestine --> increase absorption
Antioxidant peptides --> decrease production of reactive oxygen species (ROS) --> protect osteoblasts from H2O2-induced oxidative stress
Collagen-derived peptides --> beneficial effects on proliferation, differentiation, and formation of a mineralized bone matrix of osteoblasts & possibly affects activation of pathways related to collagen synthesis
Prebiotics:
Maintaining skeletal health through:
- improving mineral absorption and bioavailability
- preventing bone loss
- anti-inflamamtory effects
- anti-inflamamtory effects
Mechanisms:
(1) The consumption of prebiotics increases the production of SCFAs in the gut , which have been beneficially associated with calcium absorption through the involvement of several mechanisms.
(2) SCFAs could lower the intestinal pH and prevent th precipitation of calcium induced by phytates and oxalates.
(3) Consumption of SCFAs could enhance the properties of epithelial barrier and improve the morphological characteristics of the intestine such as crept depth, blood flow etc, thus providing a wider intestinal surface and increased absorption of calcium in the gut.
Bioactive peptides:
Milk-derived peptides
Lactoferrin (40 mg/d) --> shown to increase BMD in healthy adult women. Mechanism proposed to be
mediated through inhibition of osteoclast-mediated bone resorption by the MBP supplementation
Casein phosphopeptides (CPP)
regarded calcium absorption promotors owing to their interaction with L-type and transient receptor (TRPV6) calcium channels
Phytoestrogens:
Isoflavones, lignins and coumestans
The health benefits of soybean photo-estrogens in healthy postmenopausal women are subtle and even some well-desgined studies do not show protective effects
Future studies should focus on high-risk postmenopausal women, especially in the areas of diabetes, CVD, breast cancer and bone health
Free fatty acid receptor 4 (FFAR), a G-protein coupled receptor, is expressed in the osteoblasts, osteoclasts, and MSCs.
Dietary proteins:
Proteins, particularly collagen, make up 22% of the bone mass.
4 underlying mechanisms supporting the positive ereationship between high protein intake and bone health:
(1) Increased dietary protein intake could increase the levels of serum insulin-like growth factor (IGF-1)
(2) There was a positive association between dietary protein intake and intestinal calcium absorption
(3) High protein intake could increase lean body mass in postmenopausal women and physical performance
(4) Dietary protein consumption could effectively provide amino acid profiles for the synthesis of collagen and non-collagen in the bone matrix
Dietary patterns
Mediterranean Diet:
(1) 85% of fats in the MD is provided by olive oil with low SFAs and high monounsaturated fatty acids (MUFAs).
(2) Numerous foods in the MD had anti-inflammatory and antioxidant activities. The increased oxidative stress and impairment of antioxidant systems were critical pathogenic factors of age-related bone loss
(3) Other components in the MD are represented by phenolic compounds, which are mainly contained in olive oil, fruits, vegetables and wine. Among the phenolic compounds, hydroxytyrosol, the major polyphenol olive oil, could prevent oxidative damage via the activation of mitochondrial biogenesis and phase II detoxifying enzyme systems
Western Diet:
(1) High consumption of red meat, processed meat, refined grains, high-fat dairy products etc
(2) Averse effects of the WD on bone health could be discussed in several aspects. The poor composition of nutrients exists in the WD, especially the high consumption of protein and low intake of fruits and vegetables.
(3) A high-sugar diet exerted a detrimental effect on both bone formation and resorption, leading to a decrease in bone mass and strength, which might be attributed to the impairment of mitochondrial respiration.