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PEER REVIEW: OSTEOPOROSIS
Management and Treatment of Osteoporosis Written by Kevin McCarroll Dr Kevin McCarroll is a consultant physician and geriatrician specialising in osteoporosis at St James’s Hospital, Dublin where he is a Clinical Lead of the Bone Heath Unit. He also co-runs the orthogeriatric service and is a Clinical Senior Lecturer in Medical Gerontology at Trinity College. He is a co-investigator in the Trinity, Ulster, Dept Agriculture (TUDA) study of over 5000 patients in which research on bone health and vitamin D is being conducted.
Osteoporosis is common and affects an estimated 300,000 people poople in Ireland. It is defined as decline in bone mass associated with a microarchitectural deterioration in bone resulting in increased risk of fragility fracture. In practise, the diagnosis can be made when the lowest T score on DXA is ≤-2.5 at any of three sites (total hip, neck of femur or lumbar spine). However, a clinical diagnosis of osteoporosis can also be made without bone mineral density (BMD) measurements in patients who have a fragility fracture of the hip or spine. Fragility fracture is one that occurs from a fall from standing height or due to trauma not normally expected to cause a fracture. Osteopenia is defined when the T score is between -1.0 to < -2.5. In premenopausal females and males aged under 50, a Z score < -2.0 indicates low bone mass which may due to osteoporosis though other causes such as osteomalacia need to be considered. Who to treat? Osteoporosis therapy may in general be initiated when there is: (1) clinical diagnosis due to low trauma hip or vertebral fracture (2) diagnosis based on DXA criteria (3) high fracture risk as calcuated using tools such as FRAX (4) osteopenia with high risk of fracture. The FRAX tool can be used to estimate 10 year fracture risk with or without BMD. The threshold to start therapy varies by country and guidelines. The National Osteoporosis Guideline Group (NOGG) in the UK have established age dependent
thresholds. For example, in adults aged 70+, therapy is recommended when then 10 year fracture risk for hip is 5.4% and 20.3% for major osteoporostic fracture. In patients with no fracture history but with moderate osteopenia (T score < 1.5 -2.0) and on drugs causing bone loss (eg. aromatase inhibitors, steroids) antiresorptive therapy can be started. Factors to consider Up to 50% of fragility fractures occur in patients with osteopenia as other factors influence risk. While about 70% of bone strength relates to BMD, other factors collectively determining ‘bone quality’ are important, especially in the spine. For example, patients on steroids, aromatase inhibitors and androgen deprivation therapy have a higher risk of fracture independent of BMD resulting from their negative effects on bone quality. For recurrent fallers (≥2 per year), FRAX estimated fracture risk may be increased by 30%. Prior recent fracture (within 2 years) is a big predictor of imminent fracture. The majority (70%) of vertebral fractures do not present clinically but are associated with increased incident vertebral fracture risk by a factor of 2-5. For this reason, any previous radiological imaging which includes the spine should be reviewed. In patients at very high risk of fracture (FRAX risk 60% above treatment threshold), T score ≤ -3.5 or recent vertebral fractures, parenteral or anabolic therapy should be considered. Vitamin D / calcium and lifestyle
AUGUST 2022 • HPN | HOSPITALPROFESSIONALNEWS.IE
factors should be addressed including avoidance of smoking, alcohol in moderation and weight bearing exercise (at least 30 mins/day). Resistive exercises to improve muscle strength and balance are advised and where appropriate multidsiciplinary input to reduce falls risk. Secondary causes of osteoporosis should be looked for, especially in younger patients or those with very low T scores. Most trials of osteoporosis medications have included patients on vitamin D / calcium supplements. However, not everyone needs supplemental calcium and the dose should be tailored to the individual. In general, total calcium intake should be 1000 mg combining diet and and /or supplements. Patients should have a serum 25-hydroxyvitamin D level of at least 50 nmol/l which can usually be achieved with 800-1000 IU of vitamin D per day. Bisphosphonates First line therapy for osteoporosis is usually oral bisphosphonates which are also indicated for prevention of steroid induced osteoporosis. They reduce the risk of fractures of the hip and spine by up 50% an forearm by about 25%. However, use is contraindicated in renal impairment (<35 ml/ min), GORD and oesophageal disorders (Barretts and achalasia). Unfortunately, persistence with bisphosphonates is low at about 50% at one year, highlighting the importance of selecting the appropriate patients for treatment: avoid if difficulty remembering to take or comply with instructions (sit upright for at least 30 mins, full glass of water, no food) and if GI intolerance / malabsorption syndromes. Alendronate may have superiority over risedronate in BMD gains but there is no evidence of any difference in antifracture efficacy. Ibandronate can be taken once monthly as an alternative for some patients with mild GORD. Zolendronic acid is an alternative therapy when there are GI contraindications to oral bisphosphonates. It has also been recommended as a first line initial treatment for patients in hospital with a hip fracture and can be considered in those at very high fracture risk. It is given as a once yearly intravenous infusion
over 15-30 mins. It has similar antifracture efficacy at the hip and forearm but is superior at reducing vertebral fractures (about 70% reduction). Standard therapy is for 3 years though in patients with severe osteoporosis and high risk of fracture, it may be considered for up to 6 years. About 25% of patients experience a mild acute phase reaction after the initial infusion (musculoskeletal pain and fever) which usually resolves with simple analgesics within 72 hrs. Drug holidays, when and for how long? Bisphosphonates have a long half life in bone (10 years) with anti-resportive and anti-fracture effects persisting for a period after therapy cessation. For this reason, patients may have a break from treatment or 'drug holiday' though this needs to be closely monitored. Importantly, the concept of ‘drug holiday’ does not apply to other osteoporosis treatments where BMD drops after therapy cessation. Treatment with oral bisphosphonates is typically for 5 years and for 3 years with zolendronic acid, after which a ‘drug holiday’ should be considered. Drug holidays may be appropriate in patients who after treatment have a T score at the hip or spine of > -2.5, no recent fractures and are at lower risk of future fracture. However, in older patients at high risk of fracture (fallers, previous hip or recent fractures) or on drugs causing bone loss, therapy may need to be continued (up to 10 yrs for alendronate and 6 yrs for zoldenronic acid). Fracture risk can also be reassessed using FRAX and applying standard treatment thresholds. Drug holidays are typically for 1.5 to 3 years (18 -24 months with oral therapy and for up to 3 years with zolendronic acid) followed by repeat BMD assessment. In patients where there is a significant decline in BMD or rise in bone markers, treatment may be need to be restarted. Treatment failure This is not clearly defined but may be considered to occur when there is a decine in BMD, no improvement in bone markers or ≥2 fractures on therapy. It should always prompt an investigation into potential reasons including
