‫بسم هللا الرحمن الرحيم‬

A 55-year-old woman in good health has a screening procedure for bone mineral density (BMD)
showing significant reduction in her bone mass. She is post-menopausal for 1 year. She is given a
medication that diminishes osteoclast activity by enhancing osteoprotegerin expression. Follow up 6
months later shows an increase in her BMD. Which of the following agents did she most likely receive?

-Adrenocorticotropic hormone (ACTH)

-Direct inhibitor of RANK-Ligand

-Parathyroid hormone analogue

-Selective estrogen receptor modulator

-Vitamin D3 analogue (calcitriol)

the correct answer: Selective estrogen receptor modulator

Explanation
-Post-menopausal estrogen levels diminish, and estrogens help guard against bone loss
by favoring osteoprotegerin (OPG) expression. OPG is a decoy receptor for RANKL.

RANK (receptor activator of nuclear factor κB): receptor on osteoclasts and osteoclast
precursors, for interaction with osteoblasts

RANKL (receptor activator of nuclear factor κB ligand) : membrane-bound protein of osteoblasts that
stimulates osteoclasts by interacting with RANK to ensures fusion and differentiation into activated
osteoclasts and prevents their apoptosis

Osteoprotegerin (OPG) : a regulatory protein secreted by osteoblasts that binds RANKL

Inhibits RANK-RANKL interaction, leading to decreased osteoclast activity

-ACTH increases glucocorticoid production by adrenal cortex, which would promote osteoclast activity
and reduce bone mass.

-The bisphosphonates are direct inhibitors of RANKL and promote osteoclast apoptosis.

-The parathyroid hormone analogues will stimulate osteoblastic activity when given intermittently at
small doses but continuously will promote osteoclast activity.

-Vitamin D3 (calcitriol) aids most in calcium absorption, particularly when there is reduced renal
function.
-Normal trabecular bone, has a regular lamellar architecture. The bone lamellae form into a complex
three-dimensional structure in response to stresses of gravity and movement to provide strength and
support.

- Between the bone trabeculae are marrow spaces, seen here with hematopoietic elements and
adipocytes.
-The bone trabeculae in this slide taken from )vertebral body) are thin and sparse from osteoporosis.
Trabeculae have less complex branching, providing less three-dimensional support. This SLOW process
yields normal laboratory measurements of serum calcium, phosphorus, alkaline phosphatase, and
parathyroid hormone(PTH).

- In contrast, primary hyperparathyroidism yields increased or high normal PTH levels, with increased
calcium and decreased phosphorus.

-Osteocalcin synthesized by osteoblasts is incorporated into extracellular bone matrix, and circulating
levels correlate with osteoblast activity.

Nutritional medicine approach :

-Osteopenia is defined as less than 2.5 standard deviations below normal of bone density and
osteoporosis is defined as greater than −2.5 standard deviations of decreased bone density.

-Of interest is that the bone structure is an area that may store metal toxins and certain metals, including
lead and cadmium, which may be released during periods of bone loss, such as in menopause and
andropause.

-Conventional treatment programs will use only bisphosphonates; however, these drugs can lead to
dysfunctional bones as well as side effects affecting the jawbone.

- Consideration of the use of dietary supplementation with a series of menaquinones (MK) (vitamin K2)
in the form of MK4 and MK7 that promote healthy bone metabolsim. 
Pathophysiology from nutritional perspective:

There are many contributing factors related to loss of bone density, including :

-declining hormone levels (estradiol and testosterone),

-inflammation (including an inflammatory diet),

-lack of adequate minerals and vitamins,

-malabsorption of nutrients, such as vitamin A and D, and

-inadequate loading of bones with exercise.

Evaluation/Assessment

The most appropriate assessment tools are

-DEXA scans, which will yield the T scores and

-urinary measures of bone turnover, such as DPD and CTX. 

- the serum vitamin D25OH test, calcium, RBC magnesium, vitamin D 1,25OH, PTH, calcitonin,
osteocalcin, estradiol, and testosterone levels.

Treatment/Prevention

-Therapeutic dietary measures can include using an anti- inflammatory diet, a more alkaline diet and a
diet rich in certain minerals such as calcium, magnesium, vitamin C, and vitamin K. 

-Food sources of calcium appear safer than supplements in regard to improving bone density without
raising serum calcium too much (a risk for coronary arteries). One should have at least 500–1000 mg of
food-based calcium. The most reasonable source would be dairy unless the individual is sensitive to
dairy, in which case other calcium-rich foods can be eaten, such as collard and kale greens, broccoli,
sardines with bones, or almonds.

-If supplements are used, calcium hydroxyapatite appears to have more efficacy than calcium alone in
improving bone density.

-Vitamin D25OH serum levels should be measured and should be brought well above the minimum level.

-When treating with vitamin D3, an individual’s vitamin A status should be assessed with a blood vitamin
A retinol test. If depleted or low, vitamin A supplementation should be considered.
-Weight-bearing exercise should always augment any dietary approach.

-Strong consideration should be given to assessment of estradiol and testosterone.

Thank you so much.

Do your best to everyone around you starting with yourself.