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 Table of Contents  
TOPICAL REVIEW
Year : 2019  |  Volume : 14  |  Issue : 1  |  Page : 57-60

Current treatment of osteoporosis


Department of Rheumatology and Medicine, Velammal Medical College Hospital and Research Institute, Madurai; Department of Rheumatology and Medicine, Shifa Hospitals, Tirunelveli, Tamil Nadu, India

Date of Web Publication14-Mar-2019

Correspondence Address:
Dr. Subramanian Nallasivan
Assistant Professor and Consultant Rheumatologist, Velammal Medical College Hospital and Research Institute, Madurai, Tamil Nadu
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/injr.injr_74_18

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  Abstract 


Osteoporosis is ever increasing as life expectancy continues to increase across the world. Hypovitaminosis D has been found to be prevalent even in children and adults, and hence, it is imperative to educate the public on the nutrition for bone health. “Love your bones and joints” was the slogan by the World Health Organization to increase the awareness among the public. Bone density is assessed by Dual Energy X-ray Absorptiometry scan and the T score system. Although biomarkers have been studied in research, their clinical utility is still elusive. Regular exercise and adequate intake of Calcium and Vitamin D are important to maintain bone health. Bisphosphonates are the first line drugs in the management of osteoporosis both for primary and secondary prophylaxis. Second-line drugs include denosumab, teriparatide, and newer drugs such as abaloparatide, romosozumab, and calcitonin, which have found more real-life acceptance and efficacious in the long-term management of osteoporosis. Romosozumab, a monoclonal antibody may well become the ideal osteoporosis drug with effects on bone formation and resorption. Surgical treatment choices include – Vertebroplasty and kyphoplasty are being accepted in specific instances and selected centers with variable success.

Keywords: Abaloparatide, bisphosphonate, denosumab, osteoporosis, teriparatide


How to cite this article:
Nallasivan S. Current treatment of osteoporosis. Indian J Rheumatol 2019;14:57-60

How to cite this URL:
Nallasivan S. Current treatment of osteoporosis. Indian J Rheumatol [serial online] 2019 [cited 2019 Apr 25];14:57-60. Available from: http://www.indianjrheumatol.com/text.asp?2019/14/1/57/242258




  Introduction Top


Osteoporosis is a disease characterized by low bone mass with microarchitectural deterioration of bone leading to fragile bones and fractures. In India, life expectancy is 67 years and is expected to increase to 71 years by 2025.[1] In 2013, it was estimated that 50 million people in India are either osteoporotic (T-score < −2.5) or have low bone mass (T-score between −1.0 and −2.5).[2] Longitudinal studies of changes in bone mass during growth have confirmed that in girls, the greatest increases in bone mass occur between the ages of 12–15 years, compared with 14–17 years in boys.[3] Hence, children should be targeted first to raise awareness and also increase Vitamin D intake.

The awareness of osteoporosis is low in India with surveys indicating that only 10%–15% is aware of the disease. Urbanization appears to be associated with an increase in the prevalence of osteoporosis due to lifestyle changes, lower physical activity, increase in indoor living, and lower sun exposure. The 1-year mortality after hip fractures is high at 30% in the public hospitals. For both genders, exercise was equally positively associated with Bone Mineral Density (BMD).[4]

Diagnosis

The standard battery of tests for evaluating osteoporosis includes serum calcium, renal functions, 25 hydroxy Vitamin D3 levels, thyroid function tests, parathyroid hormone (PTH) levels, and alkaline phosphatase. Dual Energy X-ray Absorptiometry scan to estimate the BMD (in the lumbar spine and femoral hip) is the standard investigation for osteoporosis. The World Health Organization (WHO) guidelines on T score and Z score and Fracture risk assessment using the Fracture Risk Assessment Tool (FRAX) tool are recommended to identify high-risk patients. Drug treatment should last for 5 years and thereafter based on the risks. The decision to treat should be taken based on the risks, FRAX tools, patient preference, and benefits. Women with previous major osteoporotic fracture, those who fracture on therapy or others at high risk should generally continue therapy for up to 10 years (oral) or 6 years (intravenous), with periodic risk-benefit evaluation.

Current practice

All patients taking corticosteroids should be considered for osteoporosis prevention irrespective of the dose and duration of steroids and be given Calcium, and Vitamin D. Patients who have associated risk factors, preexisting bone loss and who are on corticosteroids for longer duration should be considered for antiresorptive therapy.[5]

Although India is a tropical country with abundant sunlight, evidence points to increasing incidence of Vitamin D deficiency, the reasons for which are multifactorial such as traditional clothing (saris, jeans, and salwar kameezes), inadequate dietary intake, poor Vitamin D fortification of food, and highly pigmented skin.[6] Vitamin D deficiency results in ineffective calcium absorption from the gut, which in turn affects the mineralization of bones.[7]

Evidence suggests pharmacologic therapy to be considered based on risk assessment either using FRAX calculator (country specific) or National Osteoporosis Foundation guidelines. The WHO in 1994 and 2004 review, recommends treatment using T scores which is well known. However, the decision to treat rests on the treating doctor and the patients risk and benefits of treatment.[8]

Although bisphosphonates are still the 1st line, newer drugs are increasingly accepted to be the part of the therapeutic armamentarium. Common drugs include alendronate, ibandronate, Risedronate, and parenteral zoledronic acid (ZOL). Rarely osteonecrosis of jaw has been reported in patients with the use of bisphosphonates and denosumab; the incidence is estimated to be 0.001%–0.01%, marginally higher than in the general population.[9]

Teriparatide subcutaneous (sc) injection daily for 18–24 months [10] or denosumab sc injection once in 6 months [11] have proven to be an effective treatment in improving BMD and reducing fracture risk.

Recent advances

In postmenopausal women with osteoporosis previously treated with oral bisphosphonates, denosumab was associated with greater BMD increases at all measured skeletal sites and greater inhibition of bone remodeling compared with ZOL acid.[11]

Tsai et al. in the DATA-HRpQCT study (Denosumab and Teriparatide Administration-high resolution QCT) found that 2 years of combined teriparatide and denosumab improves bone microarchitecture more than the individual treatments, particularly in cortical bone and hence beneficial in postmenopausal osteoporosis.[11] The use of abaloparatide sc for 18 months followed by Alendronate for 6 months improved BMD and reduced fracture risk throughout the skeleton and may be an effective treatment option for osteoporosis.[12]

When teriparatide and denosumab are discontinued following treatment, BMD abruptly decreases. The DATA Switch and DATA follow-up studies showed that in the 22 women not receiving follow-up therapy, femoral neck, total hip, and spine BMD decreased by −4.2 ± 4.3%, −4.5 ± 3.6%, and −10.0 ± 5.4%, respectively, while BMD was maintained in those who did receive follow-up antiresorptive drugs (femoral neck, total hip, and spine BMD changes of −0.6 ± 2.7%, −0.8 ± 3.1%, and −1.2 ± 4.7%, respectively, P < 0.001 for all between-group comparisons). The benefit with 4 years of intensive therapy was maintained in patients who received prompt antiresorptive therapy but not in those untreated. These results underscore the importance of timely medication transitions.[13]

Romosozumab is a monoclonal antibody that binds to and inhibits sclerostin, increases bone formation, and decreases bone resorption. Studies with romosozumab (originally known as AMG 785/CDP7851) in healthy men and women demonstrated a brisk increase in biochemical indices of bone formation accompanied by a decrease in markers of bone resorption.[14] These divergent effects of romosozumab on bone formation and bone resorption are very distinct from the antiremodeling agents.

In a study by Saag et al. the risk of nonvertebral fractures was lower by 19% in the romosozumab-to-alendronate group than in the alendronate-to-alendronate group (178 of 2046 patients [8.7%] vs. 217 of 2047 patients [10.6%]; P = 0.04), and the risk of hip fracture was lower by 38% (41 of 2046 patients [2.0%] vs. 66 of 2047 patients [3.2%]. They concluded that romosozumab treatment for 12 months followed by alendronate resulted in a significantly lower risk of fracture than alendronate alone.[15]

In a study by Cosman et al., patients were randomly assigned to receive sc injections of romosozumab (at a dose of 210 mg) or placebo monthly for 12 months; thereafter, patients in each group received denosumab (60 mg sc every 6 months) for 12 months. At 12 months, new vertebral fractures had occurred in 16 of 3321 patients (0.5%). In the romosozumab group, as compared with 59 of 3322 (1.8%) in the placebo group (representing a 73% lower risk with romosozumab; P < 0.001). At 24 months, the rates of vertebral fractures were significantly lower in the romosozumab group than in the placebo.[16]

The higher rate of serious cardiovascular adverse events in the romosozumab group raises concern that romosozumab may have a negative effect on vascular tissue.[16] Sclerostin is expressed in vascular smooth muscle and upregulated at sites of vascular calcification. Sclerostin inhibits bone formation by inhibiting the osteoblasts and increases bone resorption by increasing the production of receptor activator of nuclear factor kappa-β-ligand by the osteocytes.[17] Further studies would shed more light on this.


  Updated Management Recommendations Top


Life style

Regular exercise and muscle strengthening activities play an important role in keeping the bone health and reducing the risk of falls in the elderly. Smoking cessation will improve the bone health.[18]

Anticatabolic drugs

Adequate calcium and Vitamin D is essential. The use of drugs, such as Bisphosphonates, hormone replacement therapy, estrogen agonists, calcitonin, PTH, and denosumab, are decided as per the affordability and availability of treatment options. Major gaps still remain in the diagnosis and management of osteoporosis, thus highlighting the need for more research.[6]

Most of the drugs licensed for osteoporosis have very good effect on vertebral fracture risk reduction; however, some of them such as calcitonin, teriparatide, and ibandronate have less impact on hip fractures [Table 1] Based on the current evidence following observations can be made;
Table 1: Currently licensed drugs for osteoporosis and effects on fractures

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  1. Bisphosphonates remain the first drug of choice and parenteral ZOL acid scores over others as it is once yearly with better compliance and good for patients with gastroesophageal reflux disease [19]
  2. Second line would be either denosumab every 6 months or teriparatide for 18 months followed by bisphosphonates to reduce fracture incidence and enable better bone healing
  3. Abaloparatide and romosozumab are options for future
  4. Romosozumab may well become the ideal osteoporosis drug with effects on both pathways.


Surgery

Vertebroplasty or kyphoplasty is still effective in selected patients. Vertebral augmentation or vertebroplasty is effective for patients with subacute pain, focal tenderness, and edema on MRI concordant with the fracture.[20] During the last 10 years, increasing evidence points to the success of vertebroplasty and NICE (UK) have accepted in selected patients. However, Cochrane review by Buchbinder et al. does not support vertebroplasty in routine practice.”[21]


  Conclusion Top


Bone health can be maintained by achieving peak bone mass in adolescence, maintaining strong bone with Vitamin D and prevention of bone loss by aerobic and other exercises.

Evidence suggests the emergence of new anabolic drugs and biologics with the sequential approach of drug treatment [22] to prevent fractures and improve long-term health. The development of drugs such as abaloparatide and romosozumab will add further to the therapeutic armamentarium.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Government of India: Ministry of Home Affairs Office of the Registrar General and Census Commissioner, India; 2011. Available from: http://www.censusindia.gov.in/. [Last accessed on 2015 May 03].  Back to cited text no. 1
    
2.
Mithal A, Kaur P. Osteoporosis in Asia: A call to action. Curr Osteoporos Rep 2012;10:245-7.  Back to cited text no. 2
    
3.
Theintz G, Buchs B, Rizzoli R, Slosman D, Clavien H, Sizonenko PC, et al. Longitudinal monitoring of bone mass accumulation in healthy adolescents: Evidence for a marked reduction after 16 years of age at the levels of lumbar spine and femoral neck in female subjects. J Clin Endocrinol Metab 1992;75:1060-5.  Back to cited text no. 3
    
4.
Tønnesen R, Schwarz P, Hovind PH, Jensen LT. Physical exercise associated with improved BMD independently of sex and Vitamin D levels in young adults. Eur J Appl Physiol 2016;116:1297-304.  Back to cited text no. 4
    
5.
Datta S. Steroid induced osteoporosis. Med Update 2012;22:328.  Back to cited text no. 5
    
6.
Khadilkar AV, Mandlik RM. Epidemiology and treatment of osteoporosis in women: An Indian perspective. Int J Womens Health 2015;7:841-50.  Back to cited text no. 6
    
7.
Christakos S, Dhawan P, Porta A, Mady LJ, Seth T. Vitamin D and intestinal calcium absorption. Mol Cell Endocrinol 2011;347:25-9.  Back to cited text no. 7
    
8.
Kanis JA. On behalf of the World Health Organization scientific group. Technical report. On Assessment of Osteoporosis at the Primary Health-Care Level. United Kingdom: World Health Organization Collaborating Centre for Metabolic Bone Diseases, University of Sheffield; 2007.  Back to cited text no. 8
    
9.
Svejda B, Muschitz Ch, Gruber R, Brandtner Ch, Svejda Ch, Gasser RW, et al. Position paper on medication-related osteonecrosis of the jaw (MRONJ). Wien Med Wochenschr 2016;166:68-74.  Back to cited text no. 9
    
10.
Tsai JN, Uihlein AV, Burnett-Bowie SM, Neer RM, Derrico NP, Lee H, et al. Effects of two years of teriparatide, denosumab, or both on bone microarchitecture and strength (DATA-HRpQCT study). J Clin Endocrinol Metab 2016;101:2023-30.  Back to cited text no. 10
    
11.
Miller PD, Pannacciulli N, Brown JP, Czerwinski E, Nedergaard BS, Bolognese MA, et al. Denosumab or zoledronic acid in postmenopausal women with osteoporosis previously treated with oral bisphosphonates. J Clin Endocrinol Metab 2016;101:3163-70.  Back to cited text no. 11
    
12.
Cosman F, Miller PD, Williams GC, Hattersley G, Hu MY, Valter I, et al. Eighteen months of treatment with subcutaneous abaloparatide followed by 6 months of treatment with alendronate in postmenopausal women with osteoporosis: Results of the ACTIVExtend trial. Mayo Clin Proc 2017;92:200-10.  Back to cited text no. 12
    
13.
Leder BZ, Tsai JN, Jiang LA, Lee H. Importance of prompt antiresorptive therapy in postmenopausal women discontinuing teriparatide or denosumab: The denosumab and teriparatide follow-up study (DATA-follow-up). Bone 2017;98:54-8.  Back to cited text no. 13
    
14.
Padhi D, Jang G, Stouch B, Fang L, Posvar E. Single-dose, placebo-controlled, randomized study of AMG 785, a sclerostin monoclonal antibody. J Bone Miner Res 2011;26:19-26.  Back to cited text no. 14
    
15.
Saag KG, Petersen J, Brandi ML, Karaplis AC, Lorentzon M, Thomas T, et al. Romosozumab or alendronate for fracture prevention in women with osteoporosis. N Engl J Med 2017;377:1417-27.  Back to cited text no. 15
    
16.
Cosman F, Crittenden DB, Adachi JD, Binkley N, Czerwinski E, Ferrari S, et al. Romosozumab treatment in postmenopausal women with osteoporosis. N Engl J Med 2016;375:1532-43.  Back to cited text no. 16
    
17.
Wijenayaka AR, Kogawa M, Lim HP, Bonewald LF, Findlay DM, Atkins GJ, et al. Sclerostin stimulates osteocyte support of osteoclast activity by a RANKL-dependent pathway. PLoS One 2011;6:e25900.  Back to cited text no. 17
    
18.
Hollenbach KA, Barrett-Connor E, Edelstein SL, Holbrook T. Cigarette smoking and bone mineral density in older men and women. Am J Public Health 1993;83:1265-70.  Back to cited text no. 18
    
19.
Maricic M. The role of zoledronic acid in the management of osteoporosis. Clin Rheumatol 2010;29:1079-84.  Back to cited text no. 19
    
20.
Wali AR, Martin JR, Rennert R, Resnick DK, Taylor W, Warnke P, et al. Vertebroplasty for vertebral compression fractures: Placebo or effective? Surg Neurol Int 2017;8:81.  Back to cited text no. 20
  [Full text]  
21.
Buchbinder R, Johnston RV, Rischin KJ, Homik J, Jones CA, Golmohammadi K, et al. Percutaneous vertebroplasty for osteoporotic vertebral compression fracture. Cochrane Database Syst Rev 2018;4:CD006349.  Back to cited text no. 21
    
22.
Reginster JY, Al Daghri N, Kaufman JM, Bruyère O. Effect of a sequential treatment combining abaloparatide and alendronate for the management of postmenopausal osteoporosis. Expert Opin Pharmacother 2018;19:159-61.  Back to cited text no. 22
    



 
 
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