Osteoporosis is an ubiquitous disease affecting approximately 1.2 million Australians and 200 million people worldwide and is known to significantly impact quality of life.^{1, 2} 

With peak bone mass occurring around 20 years of age, and lifestyle factors influencing between 2040% of adult peak bone mass, it is important to optimise lifestyle and nutritional factors to support bone mass and reduce the risk of osteoporosis.³

Fig. 1 Bone mass across the lifespan with optimal and suboptimal lifestyle choices.³

The process of bone modelling commences during foetal development and continues until the second decade of life. Other characteristics, such as cortical density and structural strength, which determine bone dimension and thickness, can continue into the third decade of life.³ 

Signalling pathways influencing bone health

The receptor activator of nuclear factor-kappaB (RANK)/ RANK ligand (RANKL)/ osteoprotegerin (OPG) signalling pathway is a key system in bone remodelling, this is due to its function in the regulation and differentiation of osteoclasts.⁴ RANKL/OPG ratio is an important factor in bone mass and skeletal integrity; OPG protects the skeleton from disproportionate bone resorption via binding to RANKL and blocking its binding to RANK, preventing excessive osteoclast differentiation.⁵  

Implications of oestrogen in bone health

The role of oestrogen in bone remodelling is fundamental in this pathway due to its effects on upregulation of transforming growth factor β (TGF-β) and OPG. The decline in oestrogen during menopause leads to an increase in inflammatory cytokines, tumor necrosis factor alpha (TNF-α), interleukin 1 (IL-1) and interleukin 6 (IL-6). TNF-α promotes expression of RANKL and consequently an increased activity of osteoclasts, promoting bone turnover and reducing bone mineral density (BMD).⁴ 

Due to the drop in oestrogen seen in menopause, it is important that young females include dietary and lifestyle factors which support the development of peak bone mass to help reduce the risk of bone fragility and osteoporosis in later life.

Fig 2. The role of estrogens in bone remodelling.⁴

Diet and lifestyle considerations in the younger population 

Carbonated beverages

An emerging factor affecting the development of healthy bone mass is the intake of carbonated and caffeinated beverages. Several cross-sectional studies have found a strong link between carbonated beverage and cola consumption and reduced bone mineral content (BMC), areal bone mineral density (aBMD), or bone strength, leading to a higher fracture risk. This is thought to be due to increased urinary calcium and excessive intake of phosphorus.³

Carbonated beverages and increased fracture risk

To date there have been several notable studies examining the effects of carbonated beverages on the development of healthy bone mass during childhood. A population-based, case-control study found that wrist and arm fractures in children was significantly associated with cola drink consumption. Additionally, a 4-year prospective study found similar results with researchers concluding that carbonated beverage consumption is associated with increased fracture risk. ^6-8 Sedentary activities in children (television, computer, and video watching) were also positively associated with increased fracture risk. ⁹ 

Eating patterns

Several clinical trials have confirmed the correlation between anorexia nervosa and low BMD.¹⁰ This may be in part due to adipose tissue-derived adipokine, omentin-1. Omentin-1 has been shown to negatively affect bone metabolism by inhibiting bone formation and resorption, this is thought to be via its effect on upregulating the osteocalcin/ C-terminal telopeptide (OC/CTx) ratio in persons with anorexia nervosa.¹¹

In contrast childhood obesity has also been linked to compromised BMD, via different mechanisms, including:

• Increased sedentary behaviours and reduced physical activity.
• Increased consumption of carbonated beverages, lower intake of fruits, vegetables, and calcium rich foods.
• Elevated levels of proinflammatory cytokines (TNF-α, IL-1 and IL-6) which mediate osteoclast differentiation, promoting bone resorption.¹²

Diet and lifestyle factors supporting BMD

Physical activity

Mechanical loading from physical activity is an important lifestyle factor in preventing osteoporosis as it provides stimulus to support the development of healthy bone mineral density and can support bone modelling at all ages.³ Using physical activity alongside a healthy diet and tailored supplement program rich in calcium, vitamin D, vitamin K and additional macro and micro-nutrients required for bone and connective tissue is important to assist in reducing fracture risk.

Key nutrients to support bone health and reduce osteoporosis

Vitamin D and vitamin K may be key nutrients in regulating the RANKL/RANK/OPG pathway with studies showing vitamin D can upregulate OPG/RANKL ratio while inhibiting inflammation-induced osteoclastogenesis.^13,14 Vitamin D was also demonstrated to be effective in reducing the production of RANKL and the secretion of TNF-α, IL-17, and IL-6, regulating bone resorption.¹⁵

Similarly, vitamin K2 has been shown to suppress bone resorption and improve osteoblast differentiation by enhancing expression of OPG while inhibiting expression of RANKL on osteoblasts/osteoclasts.¹⁶     

Vitamin K

A systematic review focusing on the use of vitamin K2 in osteoporosis patients found vitamin K2 was able to prevent vertebral fractures by 60%, hip fractures by 77% and other fractures by 81%.¹⁷ This was further supported in a clinical trial involving 241 osteoporotic patients, assigned either vitamin K2 (45 𝜇gm/day) with calcium or calcium and placebo. Results found vitamin K2 + calcium improved bone density with 65% fewer fractures compared to the calcium + placebo group.¹⁷

Fig 3. Cellular mechanisms of vitamin K2 in promoting bone formation and inhibiting bone resorption.¹⁸ 

This may be due to the multiple roles, vitamin K plays in supporting bone health, including:

• Stimulates osteoblastogenesis and reduces osteoclastogenesis.¹⁶
• Supports osteogenic differentiation of bone marrow mesenchymal stem cells.¹⁹
• Supports synthesis of osteocalcin.¹⁷
• Enhances matrix Gla protein synthesis in cartilage.¹⁷
• Transports calcium and improves bone mineral density.¹⁷
• Enhances expression of OPG while inhibiting expression of RANKL on osteoblasts/osteoclasts.¹⁶ 

Vitamin D

Adequate vitamin D levels are required to regulate serum calcium levels, stimulate gastrointestinal calcium absorption and promote normal bone metabolism.²⁰ Vitamin D deficiency can impair blood calcium levels, resulting in an increase in parathyroid hormone (PTH), contributing to bone resorption.²⁰ 

Vitamin D requirements for bone health:

• 25(OH)D levels of at least 50 nmol/L are required for normalization of PTH levels, to minimise the risk of osteomalacia and for optimal bone cell function.²⁰
• 25(OH)D concentrations of 30–50 ng/mL (75–125 nmol/L) are beneficial for overall health.^21,22
• Doses between 1,500 – 5,000 IU of vitamin D for 6-12 weeks is recommended to amend deficiencies.^{21, 22}

Calcium and Vitamin D

The benefits of calcium and vitamin D on bone health has been extensively studied with multiple reviews and meta-analysis highlighting their positive effects on bone health.^{23, 24} While calcium supplementation has been shown to improve bone density and reduce total fracture incidence, after 2 years of administration positive effects did not persist upon ceasing calcium supplementation, showing that adherence is crucial for effective therapy.^{25, 26}

Bone health research suggests that calcium should be supplemented along-side vitamin D in order to adequately reduce fracture risk.²⁵ Furthermore, the lifetime risk of developing osteoporosis is reduced by 25% with the daily use of 800 IU of vitamin D, 45 𝜇g of vitamin K (as MK-4) and 1200mg of calcium.¹⁷

Conclusion

Osteoporosis is a condition with a wide-reaching impact on quality of life. While we commonly associate this condition with elderly patients, it is important to consider bone health in our younger patients with poor dietary and lifestyle choices as this can contribute to disease progression of osteoporosis in later life. 

References

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