ICD-9 Codes: Generalized, 733.0; postmenopausal, 733.1; idiopathic 733.02; drug induced 733.09; dis-use 733.03;  osteopenia 733.90

ICD-10 Codes: M80 – M82;  Age related osteoporosis without fracture M81.0

What is it?

Osteoporosis is a reduction in bone mass with microarchitectural deterioration leading to bone fragility and fracture.

What causes it?

Many causes have been identified (Table A) including excess glucocorticoids (Cushing’s or iatrogenic), deficiencies of sex steroids in men and women, lack of gravitational force (immobilization or space flight), chronic active inflammation, or nutritional deficiencies (calcium, vitamin D) which may result from dietary lack or malabsorption.  Estrogen deficiency mediates enhanced bone loss through production of cytokines including IL-1.

Pathology:  Bone mineral and organic phases are structurally normal and present in normal proportions. The primary defect is in bone remodeling where there is an imbalance between bone resorption and formation. Factors that influence bone remodeling (e.g, estrogen deficiency, steroid use, immobilization, etc.) can increase osteoclast activity, uncoupling the bone remodeling process and affecting the total quantity of bone. Histologic findings show reduction in trabecular thickness. Cytokines that have been associated with bone remodeling include: IL-1, IL-6, IL-11, TGF, RANKL, and TNF.

Who gets it?

Over 10 million Americans are affected by osteoporosis, and 1.5 million osteoporotic fractures occur annually. Postmenopausal women represent the largest patient group. Men older than age 60 may show decreasing bone density, although increased fracture risk does not appear until after age 70. The risk of vertebral compression fracture and hip fracture in postmenopausal white women is nearly 20%. Black individuals tend to have greater bone density and are thus at a much lower risk of osteoporotic fractures. Patients of all ages who are treated with chronic glucocorticoids have accelerated bone loss.

Table A.  Risk Factors for Development of Osteoporosis
Female gender
Hypogonadal (both genders)
Postmenopausal women
Small skeletal mass  (Weight < 127 lbs.)
White race
Lifestyle habits: tobacco, alcohol, lack of exercise, malnutrition
Medications: glucocorticoids, anticonvulsants, lithium, aromatase inhibitors, thyroid preparations, heparin, cyclosporine
Comorbid conditions: hyperparathyroidism, hyperthyroidism, diabetes mellitus, malabsorption syndromes, Cushing syndrome, rheumatoid arthritis, multiple myeloma, alcoholism

What are the symptoms?

At the outset, osteoporosis is clinically silent. In later stages, fracture may occur in the vertebral bones, with resulting wedge-shaped deformities that can cause radiating pain and contribute to formation of an exaggerated kyphosis, known as the dowager ’s hump. Other sites at risk of fracture include the forearm (Colles fracture) and the hip. Fractures in osteoporotic ribs may be induced by coughing and can cause considerable pain. Cortical bone stress fractures may occur in the lower extremities or feet.

Uncommon Manifestations: Loss of height, a protruberant abdomen, and decreased pulmonary capacity may be signs of osteoporosis. Vertebral fractures can rarely cause spinal cord compromise. Although bisphosphonate use has been reported to increase the risk of atrial fibrillation or esophageal cancer, FDA analysis has failed to establish any substantive risk for atrial fibrillation or esophageal cancer with chronic bisphosphonate use.

Complications:  Osteonecrosis of the jaw (ONJ) is a rare event in OP patients receiving bisphosphonates with an adverse event risk ranging from 1:4000 to 1:250,000. The associate between oral bisphosphonates and ONJ is a remote one with no clear relationship between the risk and duration of therapy.  Another rare event is the unusual occurrence of  femoral shaft fracturs with “atypical” features suggesting a brittle bone-type fracture.  This has primarily been reported in patients receiving long-term antiresorptive therapy (average duration 7 years). Two studies suggest that risk increases with long-term bisphosphonate therapy, with a risk of 5-100 fractures per 100,000 patients exposed for 5-10 years.   For those with a low to modest fracture risk, interruption of treatment for 1-3 years (“drug holiday”) is appropriate after 3-5 years of chronic therapy.

How is it diagnosed?

Osteoporosis may be suspected based on routine conventional radiography; note that about 25-50% of loss in bone mass must occur to detect osteopenia on x-rays. While radiographs are an insensitive measure of bone density, occult fractures may be detected. Bone densitometry (e.g., DEXA scan) measurements are diagnostic (see p. 66).  DEXA should include two sites: the hip and lumbar spine. DEXA with vertebral fracture assessments (VFA) enhances the ability to detect previous fractures. Indications for bone density testing are listed in Table B.  Standard lab tests that are important in assessing patients for secondary causes of osteoporosis include: CBC, CMP, TSH, alkaline phosphatase, 25- OH vitamin D, measurement/estimated 24 hour urinary calcium. Consideration can be made for evaluating the ESR, intact PTH, SPEP/UPEP based on clinical suspicion. Men with osteoporosis should have testosterone levels checked. Biochemical markers of bone turnover are available but not routinely done.

Table B. ISCD Position Statement: Indications for Bone Density Testing
All women > 65 years old
All postmenopausal women <65 yrs. with 1 or more risk factors (low body weight, prior fracture, high risk medication use, disease associated with osteoporosis)
Men > 70 years old
Men <70 y.o with 1 or more risk factors
Previous fragility fracture
Osteopenia or vertebral abnormalities documented on radiographs
Anyone being treated, to monitor treatment effect
Anyone not receiving therapy where evidence of bone loss would lead to treatment

Keys to Diagnosis: An early diagnosis can be made (before fractures occur) if an individual in the at-risk population (Table A) is identified and routinely assessed by bone densitometry or radiographic studies.

Differential Diagnosis: Osteoporotic fractures should be distinguished from pathologic fractures and their underlying abnormalities (i.e., bony metastases). Primary hyperparathyroidism causes accelerated bone loss in primarily cortical bone, especially the hip. Osteomalacia may be associated with low levels of 25- hydroxyvitamin D and phosphate and appear like osteoporosis on bone density. Bone biopsy may be required for definitive diagnosis of osteomalacia. Heritable disorders of connective tissue, including Marfan’s and Ehlers-Danlos syndromes, are often associated with osteoporosis.

How is it treated?

The primary goal of therapy should be prevention of fractures.
—General measures: Lifestyle adjustments should include cessation of tobacco use and of excessive intake of alcohol. Weight-bearing exercise is recommended. Frail and elderly patients with high fracture risk should have a living situation that does not require use of stairs, and ambulation aids should be used if necessary.
—Drugs:  Calcium (1,000–1,500 mg/day) and vitamin D supplementation are recommended for all. In postmenopausal women, long-term hormone replacement with conjugated estrogens (with or without progesterone) is effective but has been associated with other unacceptable (cardiovascular, breast cancer) risks. Other options include the use of raloxifene (selective estrogen receptor modulator), bisphosphonates (i.e., alendronate, risedronate, zolendronate, ibandronate), teriparatide (synthetic parathyroid hormone), and denosumab (RANKL inhibitor.   The recent release of daily subcutaneous injections of teriparatide (synthetic parathyroid hormone) has added to the arsenal against osteoporosis. The use of sodium fluoride is controversial. Combinations of these therapies are being studied, data have not proven any benefits over monotherapy. The use of strontium and calcitonin is controversial. Although, calcitonin may have analgesic properties, and has been used in the treatment of painful fractures.

Table C.  2010 ACR guidelines on prevention and management of glucocorticoid induced osteoporosis (GIO)
1. Use the lowest effective steroid dose for the shortest duration possible
2. Counsel on lifestyle modifications (weight bearing activities, tobacco cessation, avoid alcohol > 2 drinks/day)
3. Assess fall risks
4. Obtain baseline (and consider annual measurements) of height, DEXA, and 25-OH vitamin D level
5. Assess for prevalent fragility fractures
6. Start calcium intake 1200-1500 mg/day, with vitamin D 800-1000 IU daily
7. Treat with osteoporosis medications if postmenopausal female (or male > 50 yrs at risk for fracture) receiving glucocorticosteroid >3 months >7.5 mg/day*:

  • Low risk patients: alendronate, risedronate, zolendrate
  • Medium risk patients: alendronate, risedronate, zolendrate
  • High risk patients: alendronate, risedronate, zolendrate, teriparatide

*Any individuals with previous fragility fractures on glucocorticoids >1 month should be considered for therapy as above.

Surgery: Surgery is rarely required except to stabilize fractures. Early detection of vertebral collapse may be managed with vertebroplasty (high pressure infusion of cement into collapsed vertebra) or kyphoplasty (vertebral height restored using an intravertebral balloon followed by cement) to relieve pain and restore vertebral morphology. Bone biopsy is occasionally required to confirm that other conditions (osteomalacia, hyperparathyroidism, Paget disease, metastatic disease) are not present.

What is the outlook?

Fractures (especially hip fractures) in elderly patients are associated with significant morbidity and mortality. Improved awareness and a wide range of available treatments for osteoporosis may significantly change the course of this disease.

Adapted from: RheumaKnowledgy


2014 NOF Clinician’s Guide to Prevention and Treatment of Osteoporosis

The Clinician’s Guide to Prevention and Treatment of Osteoporosis was developed by an expert committee of the National Osteoporosis Foundation (NOF) in…
Crystal ball gazing, the fine art in modern science: OSTEOPOROSIS
As medicine moves from fixing problems to preventing them, like from fixing fractures to preventing Osteoporosis, the clinician has to finesse the art of predicting who is most at risk, so as to channel finite resources to such, and also to limit possible side-effects which are inherent to any treatment.
In Osteoporosis, there are 3 key questions:
1) Who to screen (with BMD)?
2) Who to treat?
3) Who to pause treatment (drug holiday)?
I did not consider “Treat with what?” as a major conundrum (as is in RA) because the agents currently available have fairly similar efficacy-risk-cost (generics not considered) considerations, with numbers-needed-to-treat/harm (NNT/NNH) balanced out.
This 2014 NOF guidelines help to answer 1) & 2). 3) with regards to bisphosphonates was tackled in yesterday’s post.

IOF: National & Regional Osteoporosis Guidelines

An overview and directory of national osteoporosis treatment and management guidelines around the world.

Every region and country has formulated its own set of guidelines on Osteoporosis screening and treatment that best serves their particular population’s risk profile, taking into account the available resources for undertaking such programmes nationally.
In answer to the question “Who to treat?”, most if not all agree that FRAX is now adequately refined and nuanced in accounting for most fracture risk factors, and well contextualised and validated in the various population groups.
What is not universally agreed is the 10-year probability of hip or major fracture thresholds: what percentage is too high and should therefore deserve treatment? In reimbursement markets, this is an arbitrary number for health economists to decide. In a self-paying market, it’s a consultative and relational art between the doctor and the patient, much like that between a financial advisor and the client.

MOH: Osteoporosis CPG

A scientific meeting to launch the guidelines was organized by the Ministry of Health and the Osteoporosis Society (Singapore) , on 4 April 2009. You can download copies of the slides and recordings of the speeches by clicking on the following links:

These are Singapore’s Osteoporosis clinical practice guidelines. The useful recommendation is the simple tool, OSTA, to answer the question “Who to screen?”
They were issued in 2009, so FRAX was not mature then. It’s time to update the SG guidelines.

FRAX has 2 major shortcomings, as I see it.
Firstly, it’s unwieldy. You need either an online computer or a paid app to key in a list of data. Then you get 2 percentages. Then the patient asks what the numbers mean. If your answer went something like, “you have a 10-year probability of hip fracture of x% and a major non-hip fracture of y%”, your computer or smartphone had just taken over your job. You see the disconnect. It reminds me of the trilogy (in 4 parts), “The Hitchhiker’s Guide to the Galaxy” (betraying my vintage): when the question, “What is the answer to life, the universe and everything?” was asked of the supercomputer Deep Thought, and the answer came out as “42”.
But I digress. The bigger problem is that FRAX does not take falls propensity into consideration. Many fragility fractures do not occur if patients do not fall (so there is no pressing need to treat a bedbound frail elderly). This shortcoming was admitted by the FRAX group in their 2011 position statement.