Currently, every 8th elderly male and 3rd elderly female is osteoporotic. But with the advancement of diagnostic and treatment modalities, osteoporosis is a very well treatable condition. In this article, we cover diagnosis, investigations, therapeutics, and other management protocols for osteoporosis patients.

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Osteoporosis and fragility fractures are some of the common modifiable causes of morbidity and mortality in the elderly. The prevalence of osteoporosis is increasing because of a sedentary lifestyle.

Osteoporosis is characterised by decreased mechanical bone strength due to loss of normal bone mineral density, thereby increasing the risk of fragility fracture. It is an asymptomatic condition that often remains undiagnosed and usually manifests with acute pain secondary to low-trauma/low-velocity fracture of the hip, spine, proximal humerus, pelvis and wrist.

WHO has defined osteoporosis in terms of bone mineral density T score measured by Dual Energy X-ray Absorptiometry. It is defined as:

• T score of -2.5 or less in postmenopausal women or men aged >65 years. For other populations, a Z-score should be used to define osteoporosis
• T score ranging between -1 to -2.5 is termed osteopenia
• T score more than -1 is normal

Postmenopausal osteoporosis is attributed to oestrogen deficiency, while age-related is secondary to the normal ageing process in men and women. Both oestrogen deficiency and ageing contribute to an additive effect.

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Risk factors

1. Modifiable risk factors
   1. Smoking
   2. Chronic alcoholism
   3. Inadequate dietary calcium and vitamin d supplementation
   4. Low body mass index
   5. Physical inactivity
   6. Hypogonadism
   7. Chronic glucocorticoid use
   8. Treatment of chronic systemic diseases
2. Non-modifiable risk factors
   1. Age
   2. Sex
   3. Race

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Diagnosis

Currently, multiple modalities are available for diagnosing osteoporosis ranging from conventional radiography, computed tomography and dual-energy X-ray absorptiometry (DEXA scan).

1. DEXA scan is currently the gold standard mode of diagnosis, although they have several disadvantages like spurious report values for patients with spinal deformities or past fractures or spinal surgeries. It is also not suitable for the paediatric population and short-statured adults.
2. BMD T or Z score does not predict the risk of fracture.

Various tools are available that can help in predicting fracture risk.

1. The most commonly used tool is FRAX (Fracture Risk Assessment) Score released by WHO in 2008. It can predict overall fracture risk and at specific sites i.e spine, hip, forearm. It also helps in making clinical decisions for pharmacotherapy.
2. Scoring can be done with or without BMD - DEXA score. It includes a basic demographic profile of a patient (age, sex, BMI) clinical history of any fragility fracture, risk factors like smoking, alcohol and glucocorticoid use and history of any chronic systemic disease like rheumatoid arthritis. This scoring-based calculator is available online. The higher the percentage score, the more the risk of fracture. The major disadvantage is that it doesn't consider pharmacotherapy and can under or overestimate risk.

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How to approach osteoporosis?

1. A thorough clinical history, history of fractures, physical examination (look for Dowager's hump, shortening of height etc) is recommended for all.
2. Assessment for FRAX score is recommended for all as initial screening and evaluation.
3. Screening with DEXA scan (preferably spine, hip and forearm) is recommended in the following situations:
   1. All postmenopausal women of age >65 years and males 70 years
   2. Postmenopausal women of any age with multiple risk factors and males aged 51-59 with multiple risk factors
   3. All males and females aged >50 years with a history of fractures or on medication associated with bone loss (glucocorticoids, anticonvulsants, diuretics, PPIs etc).
4. Exclude secondary causes of osteoporosis with the help of clinical history, drug history, physical examination, serum calcium, phosphorus, alkaline phosphatase, TSH, parathormone level, Vitamin D level, urine and serum protein electrophoresis, Inflammatory markers like ESR and CRP.
5. Bone turnover markers like osteocalcin or N or C type collagen degradation peptides can be used as biomarkers for response assessment but are not commercially available widely.
6. The pharmacotherapeutic decision is taken based on the following conditions:
   1. T score - 2.5 or less.
   2. T score of 1 to 2.5 with FRAX score - risk score more than 20% for any fracture.
   3. T score 1- 2.5 and FRAX scores suggest the risk of hip fracture >/= 3%.
   4. T score of 1 -2.5 with fragility fracture of the proximal humerus, distal forearm or pelvis
7. Therapeutics might be required even without a DEXA or FRAX score in the following clinical scenario for postmenopausal women or men of age >50 years with a:
   1. History of hip or vertebral fragility fracture.
   2. History of supraphysiologic dose of corticosteroid for more than 3 months

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How to treat osteoporosis?

Treatment includes non-pharmacological and pharmacological measures.

Non-pharmacological measures

1. Increase dietary intake of calcium and vitamin D rich supplements. The recommendation for daily calcium intake is 1000 mg for males >50 years and 1200 mg daily for postmenopausal females of any age. Regarding vitamin D supplements, 400-800 IU daily should be advised for both males and females. Patients receiving glucocorticoids should receive 1000-1200 IU of vitamin D supplement daily. Excessive calcium supplements may increase cardiovascular risk, hence should be avoided
2. Advise regular physical and weight-bearing exercise.
3. Patients should be careful to avoid falls.
4. Smoking cessation should be advised.
5. Patients should be told to reduce alcohol and caffeine consumption.

Pharmacological measures

There is a wide range of therapeutics available currently for preventing progression and reducing the risk of fragility fractures. Apart from oral calcium and vitamin D supplementation, the treatment also includes selective oestrogen receptor modulators like Tamoxifen, Raloxifene, Antiresorptive medication - Bisphosphonates (Alendronate, Zoledronate etc.) and RANKL Inhibitor - Denosumab, Anabolics - Parathormone analogues like Teriparatide and abaloparatide, and newer drugs like Renosuzumab i.e Sclerostin inhibitors and Calcitonin (Human and Salmon form).

Oral bisphosphonate being the first-line agent is recommended for the treatment as well as prevention of osteoporosis. In case of oral intolerance parenteral forms like Zoledronic acid, Denosumab or Teriparatide can be considered especially in higher-risk individuals.

Follow up BMD DEXA scan recommendations

• Repeat DEXA scan should be performed at the same centres to improve accuracy and efficacy.
• DEXA T score >-1 without risk factors- Repeat after 5 to 10 years
• DEXA T score <-1 but >- 2.5 with risk factors, but not on treatment- Repeat every 2 to 4 years
• A progressive disease, T score <- 2.5 or less; on treatment- Repeat usually every 1- 2 years until stable, but can be done early if clinical situation warrants

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When to consider stopping the medication?

1. Antiresorptive medication can be given up to 3 to 5 years as per the associated risk factors for fracture. We can stop treatment i.e drug holiday- if the patient did not develop any fragility fracture while on therapy and T score improved to more than -2 and was stable. If the target is not achieved and patients have ongoing risk factors; either continuation of bisphosphonates or switching to other medication like Teriparatide or Denosumab or combination therapy with either teriparatide or denosumab needs to be considered.
2. Agents like Teriparatide should not be given for more than 1.5 years; given the increased risk of osteosarcoma and hence should be followed by sequential therapy with preferable denosumab or if not, one can consider bisphosphonates.
3. There is no drug holiday for Denosumab. It has to be continued for the long term; because of the rapid decrease in BMD after stopping.

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What are the concerning side effects of medications for osteoporosis?

1. Bisphosphonates are associated with flu-like symptoms like headache, myalgia which resolves in 1 to 2 days. It is associated with severe oesophagitis; it has to be taken on an empty stomach because of poor bioavailability. The severity of oesophagitis can be decreased by sitting upright for at least 30 minutes post-medication. Rarely it can cause osteonecrosis of the jaw, unilateral or bilateral subtrochanteric fracture, associated with higher dosage and long term treatment as with malignancies. Dose adjustment is required for kidney disease patients with eGFR <60 and should be avoided with eGFR <30. It is contraindicated in hypocalcemic patients and in those with a history of hypersensitivity reactions.
2. Denosumab can also rarely be associated with osteonecrosis of the jaw or subtrochanteric fractures. It should always be prescribed after correcting vitamin D and serum calcium because of the risk of hypocalcemia.
3. Teriparatide injection can cause injection site reaction, headache, dizziness post initial 2 to 3 injections. It is not recommended for more than 1.5 years due to the increased risk of osteosarcoma as evident in animal models.

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Osteoporosis usually has long latency and often presents with debilitating low-velocity fragility fractures. Proper screening and timely therapeutics can prevent a majority of fragility fractures. There are various clinical guidelines for screening and various therapeutics available. The above discussed are more clinically relevant aspects of available guidelines in the literature.

Disclaimer- The views and opinions expressed in this article are those of the author's and do not necessarily reflect the official policy or position of M3 India.

The author is a practising Rheumatologist from Bangalore.