How do we keep our bones young?Associate Professor Terry Diamond, Endocrinology, UNSW

Osteofragility fractures occur due to reduction in bone strength (bone density

being one variable) superimposed on trauma such as a fall. Finite bone

density is established throughout growth so that progressive calcium accrual

into the skeleton occurs from the time in utero, throughout neonatal,

adolescence, pubertal development, late into the teens. It is important to note

that approximately 40% of the skeleton is acquired during puberty (8-12 years

of age in girls and 9-13 years in boys). By the time an individual reaches 20-

30 years, the maximal amount of mineral is deposited into the skeleton. This

late and final stage of skeletal development is termed “PEAK BONE MASS”.

After achieving a peak bone density, bone mass remains relatively stable

throughout the next 20 years of life unless bone toxic agents or medical

illnesses ensue which results in bone resorption and loss. Achieving as high a

peak bone mass as possible is a pre-requisite for preventing osteoporosis in

later life. (See figure below).

BMDg/cm2

Causes of Low Bone Mass

0 10 20 30 40 50 60 70

years

Peak High

Bone

Mass Low

Early menopause

Rapid boneloser at menopause

Accelerated bone loss: disease, drugs

FRACTURE ZONE

A number of factors affect peak bone mass, but only a few are modifiable by

medical interventions. Examples include:

1. Genetics

2. Optimal nutrition and body weight

3. Pubertal timing: “ripen at the timely season”

4. Adequate exercise: “avoid a sedentary lifestyle, being a couch- or

mouse-potato”

5. Avoid toxins (tobacco, alcohol excess, medications): “stay on the

straight and narrow”

While bone mass remains stable through the 30-50’s, conditions such as premature menopause (natural, post surgery or following chemotherapy) can result in rapid bone loss and severe osteoporosis. Medical disorders (chronic heart and lung disease, immobilisation and frailty, inflammatory arthritis such as rheumatoid, liver and kidney, overactive thyroid and parathyroids and glucocorticoid drugs) occurring late in life also contribute to a significant decline in bone density.

GENETICS: “choose your parents wisely”

There are many inherited conditions resulting in osteoporosis and recurrent fractures. The most well known is Brittle Bone Disease or Osteogenesis Imperfecta. In this condition, babies fracture almost from birth resulting in deformed skeletons. They have pencil-like bones that can buckle and break under minimal trauma. The gene mutation is found on chromosome 17 and leads to a defect in collagen matrix synthesis, the scaffolding on which calcium is deposited. Other conditions also known to have osteoporosis with gene defects found on this chromosome include Marfan’s syndrome, Ehler Danlos etc.

One of the most important finding of the 90’s was the discovery of the strong relationship between bone densities in mono- and dizygotic twins. This finding set the foundation for studying genetic factors related to osteoporosis. There is now data to show that daughters of mothers with hip fractures have low bone densities in the hip. Similarly, daughters of mothers with spinal fractures have low bone densities in the spine. The future will be to unwind the genetic mutations associated with low bone mass. Until then, advocating bone mineral densities in children of parents who have fractures or osteoporosis is advised.

NUTRITION: “avoid food fads and being anorexic”

The skeleton is a bank for many minerals. Healthy bone requires a healthy diet, rich in minerals and vitamins (see figure below). Anorexia is associated with a low body fat, low endogenous estrogen and brittle bones. Gastrointestinal conditions such as coeliac disease and malabsorptive syndromes result in suboptimal vitamin D levels as well as low bone formation, predisposing to osteoporosis. The overzealous intake of soft drinks such as sodas, result in diminished dairy intake and high phosphates causing renal calcium wasting.

Calcium:

Higher consumption of calcium during the teen years is associated with

1. Greater bone mineral accretion during adolescence . Comparison of 100 teenage girls divided in 2 groups: consumption of 1400 mg. calcium/day for 18 months vs. 900 mg/day.

2. Higher bone mineral density in the postmenopausal period (Sandler et al Am J Clin Nutr 1985;42:270).

The recommended daily allowance for calcium has changed in recent months and is summarised:

Age Calcium RDA Servings4-8 years 800 mg 39-18 years 1300 mg 419-50 years 1000 mg 3-4

Despite the above, most elderly Australians only receive 300-400mg in their daily diet.

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Vitamins Minerals B12 calcium C phosphorus D magnesium K manganese

boroncopper

silicon

Vitamin D:

Vitamin D is essential for gut calcium absorption and bone mineralisation. Over the years we have evolved into a vitamin D deficient society. From wondering in the sunny tropics with sparse clothing, we have moved to temperate regions of the world where we are now fully clad, working long hours indoors and with very little sunlight exposure.

Vitamin D deficiency defined as a serum 25 hydroxyvitamin D level of at least less than 50-60 nmol/L results in malabsorption of calcium, secondary overactivity of the parathyroid glands, increased bone resorption and progressive bone loss with resultant osteoporosis. In its severe form, Rickets or osteomalacia develops so that bone fails to mineralise causing bone pain and an increased risk of minimal trauma fractures. In addition muscle weakness may ensue increasing a propensity to falling. Vitamin D also has other many pleiotropic actions. In epidemiological studies, individuals originating from regions known to be vitamin D deficient are at increased risk for immunological diseases (Type 1 diabetes, Rheumatoid arthritis, Multiple Sclerosis), metabolic disorders (Type 2 diabetes) and cancers (breast, prostate and colon).

Optimal vitamin D supplements have been shown to reduce the risk of falls and fractures in at risk individuals. The recommended daily allowance for vitamin D is suboptimal. An intake of vitamin D3 (cholecalciferol) of at least 2000 IU is recommended for bone health.

Increased bone resorption

Large bone resorption cavities “Hyperparathyroidism”

Increased unmineralised bone “Osteomalacia”

Mild Hypovitaminosis D: (serum 25OHD 25-50 nmol/L)

Severe Hypovitaminosis D : (serum 25OHD <12.5 nmol/L

Moderate Hypovitaminosis D : (serum 25OHD 12.5-25 nmol/L)

Vitamin K

Vitamin K comprises of a number of proteins.1. Hepatic proteins, which are procoagulant (II, VII, IX, X) and

anticoagulant (C, Z, S).2. Extra-hepatic proteins, which are important for, bone matrix regulation

(osteocalcin) and calcification inhibitor (matrix Gla-protein).

Vitamin K binds calcium to the hydroxy-apatite matrix. Genetic models of vitamin K deficient mouse are small, with poor cartilage and bone synthesis resulting in small brittle skeletons.

In the Framing ham study, women with the highest intakes of phylloquinone (vitamin K derivative) had lower hip fracture rates. Moreover, supplemements with vitamin K retards age and menopause-related bone loss.

Vitamin C:

Vitamin C is important for collagen synthesis and bone matrix formation. Deficiency in vitamin C results in “Scurvy” with patients presenting with gum haemorrhages, easy bruising and brittle bones. In South Africa, gold miners who ingested home made brew prepared in iron-cat pots, developed scurvy and presented with osteoporosis and osteofragility fractures.

Vitamin B12:

Today this is commonly also known as Pernicious anaemia. Elderly women with premature greying of hair develop vitamin B12 deficiency due to reduced gastric binding proteins responsible for B12 absorption. This condition may also manifest with paraesthesia in the feet (neuropathy), early onset dementia and osteoporosis due to reduced bone formation.

PUBERTY “ripen at the timely season”

Pubertal development in both sexes occurs as sex steroid production (estrogen in girls and testosterone in boys) increases thereby facilitating an increased growth spurt and mineral accrual. This occurs usually at 8-9 years of age. It is essential that the growth of long bones occur simultaneously and at variance with pubertal development. (See figure below). Any delays in puberty may have serious ramifications for bone mineral accrual. There is data demonstrating that boys with delayed puberty may have finite bone density measurements that are 1 standard deviation or 8-10% lower than boys who experience normal pubertal development. These youngsters may also be at increased fracture risk during puberty.

% P

eak

BM

D

100 90 80 70 60 50 40 30 20 10 0

8 to 9 10 11 12 13 14 15

Skull

Trunk

Upper limb

Lower Limb

Age (years)

EXERCISE: “avoid a sedentary lifestyle, being a couch- or mouse-potato”

Exercise has an important role in maintaining good cardiovascular and bone health throughout life. The muscular forces applied to the skeleton are important for bone strength building. These forces applied may be gravitational or weight bearing or site specific according to the force applied. The intensity (Strain) of the force applied is more important than the duration.

Junior Olympic weightlifters (ages 15) have greater bone densities in the spine and femoral neck than adults between the ages of 25-30. Greater bone density is likely due to the high force and rate of force production from weightlifting.

Junior gymnasts (7-8 yrs. old) have greater bone densities in load bearing sites of the sport. The magnitude of change appears to be related to volume of training. Moreover, the forces during landing from a jump in gymnastics are up to 16 times body weight.

Bone responds best to high load activities in unusual patterns. Site-specific response are evident e.g., Dominant arms of racquet sport players may have bone densities up to 20% higher than the non-dominant arm.

The effect of exercise in puberty is to achieve a higher peak bone mass, while in later life it may slow menopause- or age-related bone loss (See figure below).

CONCLUSION:

Fracture prevention is the ultimate goal of treating osteoporosis. One way of achieving this outcome is to maximise bone strength during the teens and puberty. Acquiring a high peak bone mass is vital in the prevention of osteoporosis. Some factors are remedial and can enhance calcium and mineral acquisition during this vital stage. A good diet with optimal nutrition and a well-structured exercise program can go a long way. Additional calcium and vitamin D supplements are vital during the pubertal years in boys and girls who becoming more sedentary and follow bad dietary habits.

5 Steps to Preventing Osteoporosis

Avoid harmful habits

BMD testing & medications

Active lifestyle

Regular sunshine

Healthy diet