Case Study 3: The Breaking Point

A familiar face appears over the counter of the pharmacy where you work. The patient, Angel Mendoza, is 69,
has arrived to pick up her aldendronate which was prescribed to treat her osteopenia. Osteopenia is a milder
form of osteoporosis, a condition characterized by significant bone deminearalization. Individuals with
osteoporosis have a significantly increased risk of bone fractures associated with falls. You are surprised to see
Angel on crutches, and her leg in a cast. She explains that the fracture she suffered came as the result of a
“stress-fracture” that happened as she was stepping off of a curb. You inquire if she ran out of her medication,
thinking that might have had something to do with the fracture. She assures you that she has taken the
aldendronate,,without a single missed dose, for the past 7 years. Concerned that some drug-drug interaction
might be interfering with the effectiveness of the aldendronate, you check her record of medications but find
nothing that suggest such a possibility.

1. Why are women in Angel’s age group and older are considered to be at fairly high risk for developing
osteoporosis/osteopenia?

Osteoporosis is a disease that thins and weakens the bones, causing the loss of bone mass as bones become
fragile and fracture easily. Osteopenia is a condition that occurs when the bone density is lower than normal,
causing it to be a milder form of and lead to osteoporosis. Women in Angel’s age group and older are
considered to be at fairly high risk for developing osteoporosis/osteopenia because women lose more bone mass
during and after menopause with very low levels of the hormone estrogen as higher estrogen levels before
menopause play a key role in regulating bone mass and strength through control of the activity of the
bone-forming osteoblasts and bone-resorbing osteoclasts. Estrogen helps protect bone density. In addition,
women usually have smaller, thinner, less dense bones than men and often live longer than men. Since bone loss
naturally occurs as you get older and tend to have a more sedentary lifestyle with little to no exercise, older
women are at a fairly high risk for developing osteoporosis/osteopenia.

2. Is osteoporosis/osteopenia limited to women? What other risk factors/underlying conditions are associated
with bone loss?

Osteoporosis/osteopenia is not limited to women but it affects more women than men, particularly affecting
women ages 65 or older. Other risk factors/underlying conditions associated with bone loss apart from sex
include age (the older you get, the greater your risk of osteoporosis as bone mass is lost faster than it’s created
as people age), race (greater risk of osteoporosis if you’re white or of Asian descent), family history, body
frame size (small body frames tend to have higher risk of osteoporosis due having less bone mass to draw from
as they age), low levels of estrogen and testosterone, high excessive levels of thyroid, overactive parathyroid
and adrenal glands, low calcium intake (leads to diminished bone density, early bone loss, and increased risk of
fractures), eating disorders, long-term use of corticosteroid medications (interfere with bone-rebuilding
process), celiac disease, inflammatory bowel disease, kidney or liver disease, cancer, multiple myeloma,
rheumatoid arthritis, sedentary lifestyle, excessive alcohol consumption, and tobacco use.
3. How can someone reduce their risk of developing osteoporosis?

Someone can reduce their risk of developing osteoporosis through good nutrition that includes regular and
increased intake of calcium and vitamin D as people get older and living an active, non-sedentary lifestyle with
regular exercise. Men and women between 18-50 need about 1,000 mg of calcium a day, which is increased to
1,200 mg when women turn 50 and men turn 70. Eating good sources of calcium can help reduce risk of
osteoporosis like low-fat dairy products, dark green leafy vegetables, canned salmon or sardines with bones, soy
products, and calcium-fortified cereals and orange juice. Eating dietary sources of vitamin D, including cod
liver oil, trout, and salmon, and taking vitamin D supplements will help improve the body’s ability to absorb
calcium and improve bone health in other ways. Exercise can help build strong bones and slow bone loss and
starting to exercise regularly at a young age will allow you to gain the most benefits in regards to increasing
bone strength and slowing down bone loss. Strength training exercises will help strengthen muscles and bones
in the arms and upper spine while weight-bearing exercises will help strengthen bones in the legs, hips, and
lower spine.

4. How does aldendronate prevent bone loss? Are there any other types of therapeutic agents besides
bisphosphonates that are used in the prevention/treatment of bone loss diseases?

Alendronate prevents bone loss as it is within a class of medications called bisphosphonates, which help prevent
bones from losing calcium and other minerals by slowing or stopping the natural processes that dissolve bone
tissue and thus help bones remain strong and intact. Osteoclasts are cells that degrade bone to initiate normal
bone remodeling and mediate bone loss in pathologic conditions by increasing their resorptive activity—they
eat up the aged bone so that it can be reshaped into a stronger and resilient load-bearing structure. Osteoporosis
causes osteoclasts to become more active without the hormone estrogen and results in the body breaking down
more bone than normal than it can build. As a result, alendronate, a bisphosphonate, inhibits osteoclastic bone
resorption. Alendronate attach to hydroxyapatite binding sites on bony surfaces, especially surfaces undergoing
active resorption so that when osteoclasts begin to resorb bone that is impregnated with the bisphosphonate, the
drug released during resorption impairs the ability of the osteoclasts to form the ruffled border, to adhere to the
bony surface, and to produce the protons necessary for continued bone resorption. It also reduces osteoclast
activity by decreasing osteoclast progenitor development and recruitment and by promoting osteoclast
apoptosis. There are other types of therapeutic agents besides bisphosphonates that are used in the
prevention/treatment of bone loss disease such as denosumab (used in people who can't take a bisphosphonate,
such as some people with reduced kidney function) and anabolic drugs that increase bone formation such as
romosozumab (a monoclonal antibody for treating postmenopausal osteoporosis by blocking a protein that
controls bone turnover).

5. Could aldendronate have had a role in Angel’s fracture? What is the evidence?

Alendronate could have had a role in Angel’s fracture as alendronate may cause severe bone, muscle, or joint
pain, which can be felt within days, months, or years after first taking alendronate. Since Angel didn’t stop
taking the alendronate and hasn’t missed a single dose in the last 7 years, then the fracture couldn’t have been
caused by discontinuation of the use of the drug. In addition, since her record of medications were checked and
she was found to not be taking any medication alongside alendronate, then the intended beneficial effects of
alendronate are not inhibited by interactions with other potential drugs taken by Angel. Therefore, the
possibility that alendronate could have a role in Angel’s fracture is likely since alendronate can also have
adverse effects that cause severe bone or joint pain, which means a higher likelihood of a fracture occuring.